Progel - Davol

Transcription

Progel - Davol

Progel™
Pleural Air Leak Sealant
The Only Sealant
Now FDA
FDA Approved
Approved
for use in Open
Thoracotomy,
Video-Assisted &
Robotic-Assisted
Thoracic Surgery.1
Clinically proven to seal air
leaks and reduce length of
stay by 1.9 days.2
Value Analysis Committee
Product Information Kit
1
Progel™ Pleural Air Leak Sealant Instructions for Use. M-00368.
2
Allen, Mark S. et al. Prospective Randomized Study Evaluating a Biodegradable Polymeric Sealant for Sealing
Intraoperative Air Leaks That Occur During Pulmonary Resection. Annals of Thoracic Surgery 2004; 77:17921801. Pivotal Study. Data on file.
BIOSURGERY
Proven Science. Excellent Outcomes.
Bard BioSurgery
Bard is the market leader in comprehensive soft tissue reconstruction. In addition to this extensive
suite of products, our BioSurgery franchise is delivering a growing line of enhanced sealants and
hemostatic products to complement surgical techniques across thoracic, cardiovascular, and other
surgical specialties. Bard is committed to serving our surgeons and clinicians by leveraging unique
& proprietary materials-science and continuing Bard’s focus on improving clinical outcomes for
optimal patient care.
Progel™ Pleural Air Leak Sealant has
been used in over 120,000 lung
surgeries since 20101
1
Estimated based on Q2 2015 sales data and an estimate of 1.2 4mL kits per procedure.
Progel™ Value Analysis Product Information Kit
Table of Contents
1.Product Introduction
A.Product Overview.......................................................................................... 2
B.Technology Benefits.................................................................................... 3
C.FDA Approval..................................................................................................... 4
2.Instructions for Use
A.Instructions for Use...................................................................................... 6
B.Kit Setup Instructions...............................................................................12
C.Application Instructions..........................................................................13
3.Clinical Data
A.Relevant Studies & Publications......................................................14
B.Economic Value Proposition.............................................................. 18
4.Reimbursement.......................................................................................... 20
5.Competitive Information
A.Sealant & Hemostat Indication Overview...............................21
B.Sealant Characteristic Comparison............................................. 22
C.Cross Reference Chart............................................................................ 23
6.Information for Materials Managers
A.Packaging Overview...................................................................................24
B.Storage Requirements............................................................................ 25
C.Product Order Codes............................................................................... 25
D.Product Evaluation..................................................................................... 26
7.Surgical Education................................................................................... 27
8.Bard’s Value Added Programs................................................ 28
1
1. Product Introduction
A.
Progel™ Product Overview
Designed
Progel™ is the only sealant specially designed for
the lung and its unique characteristics.
Indicated
Progel™ is the only sealant FDA approved and
indicated to treat air leaks during open, Video-Assisted &
Robotic-Assisted Thoracic Surgery.1
Clinically Proven
Progel™ is the only sealant clinically proven in a prospective,
randomized trial to treat air leak complications and reduce
hospital length of stay by 1.9 days.2
1 Progel™ Pleural Air Leak Sealant Instructions for Use. M-00368.
2 Allen, Mark S. et al. Prospective randomized study evaluating a biodegradable polymeric sealant for sealing intraoperative air leaks that occur during pulmonary resection.
Ann Thorac Surg 2004; 77:1792-1801. Pivotal trial. Davol Inc. Data on file.
2
B.
Technology Benefits
Proprietary science and technology designed to
optimize patient outcomes
Progel™ Pleural Air Leak Sealant is a specialized product that combines Polyethylene Glycol (PEG)
and Human Serum Albumin (HSA) to form the only FDA approved sealant designed for the lung
and its unique characteristics.
Polyethylene Glycol
Proprietary Progel™ PEG lends
the sealant its ability to stretch
When applied properly, Progel™ Pleural Air Leak
Sealant creates an air tight seal with the surface of
the lung to reinforce primary air leak closure. The
sealant sets up at the tissue site, binding directly to
the surface of the lung for optimal adherence. Within
2 minutes, Progel™ is strong enough to withstand
re-expansion of the lung.1,2 Once gelled, the sealant
is highly-elastic, to allow the lung to expand and
contract naturally during respiration.
The Progel™ Advantage
Optimal adherence. Strength. Flexibility.
Human Serum Albumin
Large, globular protein provides
Progel™ its adhesive strength
A unique combination of strength, flexibility and
adherence make Progel™ the only sealant specifically
designed and clinically proven to effectively treat
and reduce air leaks.3
Variable spray patterns for targeted application
The patented Progel™ Spray Tip allows for customized application from a single, easy-to-use device. By
varying the amount of hand pressure applied to the syringe, the surgeon can easily control delivery of the
sealant. Extended Spray Tips are available for use with Progel™ in both 16 cm (6") and 29 cm (11") lengths.
Stream
Minimal Hand Pressure
Increased Hand Pressure
Targeted stream for application
along staple lines and defects.
Aerosolized spray for application
to broad surfaces.
Spray
1 Progel™ Pleural Air Leak Sealant Instructions For Use. M-00368.
2 Theodore, Pierre, et al. Surgical sealant physical characteristics in vitro comparison to mitigate lung air leaks 2012. Davol Inc. In vitro testing. Data on file. In vitro test results may not correlate to clinical
performance. Five samples of each device were included in each in vitro test. The elongation modulus of Progel™ was significantly less than that of BioGlue® (p<0.05) and comparable to that of COSEAL®
and DuraSeal.™ Progel™ burst strength at time zero was significantly greater than that of COSEAL,® TISSEEL,™ BioGlue® and DuraSeal™ (p<0.05).
3
1. Product Introduction
C.
(cont.)
FDA Approval
Progel™ Pleural Air Leak Sealant is a Medical
Device approved by the FDA under the
Premarket Approval Application (PMA)
regulations in compliance with Title 21 CFR,
Part 814 “Premarket Approval of Medical
Devices.” The product contains a human
protein component (Human Serum Albumin),
is provided sterile, is listed as a Medical Device
and does not require a blood bank or tissue
bank certificate.
Progel™ Pleural Air Leak Sealant, Progel™
Extended Applicator Spray Tips, and Progel™
Applicator Spray Tips were approved under the
PMA process.
The FDA Approval letter for Progel™ Pleural
Air Leak Sealant is provided here for reference.
4
Page 3 – Pamela Misajon
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration
10903 New Hampshire Avenue
Document Control Center – WO66-G609
Silver Spring, MD 20993-0002
February 13, 2015
Ms. Pamela Misajon
Vice President, Regulatory Affairs
Neomend, Inc.
60 Technology Drive
Irvine, CA 92618
Re:
P010047/S036
ProgelTM Pleural Air Leak Sealant
Filed: August 18, 2014
Procode: NBE
Dear Ms. Misajon
The Center for Devices and Radiological Health (CDRH) of the Food and Drug Administration
(FDA) has completed its review of your premarket approval application (PMA) supplement for
the ProgelTM Pleural Air Leak Sealant (PALS). The single use ProgelTM Pleural Air Leak Sealant
device is indicated for application to visceral pleura after standard visceral pleural closure with,
for example, sutures or staples, of visible air leaks incurred during resection of lung parenchyma.
We are pleased to inform you that the PMA supplement is approved. You may begin
commercial distribution of the device as modified in accordance with the conditions of approval
described below.
The sale and distribution of this device are restricted to prescription use in accordance with 21
CFR 801.109 and under section 515(d)(1)(B)(ii) of the Federal Food, Drug, and Cosmetic Act
(the act). FDA has determined that this restriction on sale and distribution is necessary to
provide reasonable assurance of the safety and effectiveness of the device. Your device is
therefore a restricted device subject to the requirements in sections 502(q) and (r) of the act, in
addition to the many other FDA requirements governing the manufacture, distribution, and
marketing of devices.
Expiration dating for this device has been established and approved at 24 months when stored in
refrigerated conditions (2 °C to 8 °C). Expiration dating for the optional Extended Spray Tip
Applicator has been established and approved at 24 months. This is to advise you that the
protocol you used to establish this expiration dating is considered an approved protocol for the
purpose of extending the expiration dating as provided by 21 CFR 814.39(a)(7).
Continued approval of this PMA is contingent upon the submission of periodic reports, required
under 21 CFR 814.84, at intervals of one year (unless otherwise specified) from the date of
approval of the original PMA. Two copies of this report, identified as "Annual Report" and
Additional information on MDR, including how, when, and where to report, is available at
www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
In accordance with the recall requirements specified in 21 CFR 806.10, you are required to
submit a written report to FDA of any correction or removal of this device initiated by you to:
(1) reduce a risk to health posed by the device; or (2) remedy a violation of the act caused by the
device which may present a risk to health, with certain exceptions specified in 21 CFR
806.10(a)(2). Additional information on recalls is available at
www.fda.gov/Safety/Recalls/IndustryGuidance/default.htm.
CDRH does not evaluate information related to contract liability warranties. We remind you;
however, that device labeling must be truthful and not misleading. CDRH will notify the public
of its decision to approve your PMA by making available, among other information, a summary
of the safety and effectiveness data upon which the approval is based. The information can be
found on the FDA CDRH Internet HomePage located at
www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/
PMAApprovals/default.htm. Written requests for this information can also be made to the Food
and Drug Administration, Dockets Management Branch, (HFA-305), 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852. The written request should include the PMA number or docket
number. Within 30 days from the date that this information is placed on the Internet, any
interested person may seek review of this decision by submitting a petition for review under
section 515(g) of the act and requesting either a hearing or review by an independent advisory
committee. FDA may, for good cause, extend this 30-day filing period.
Failure to comply with any post-approval requirement constitutes a ground for withdrawal of
approval of a PMA. The introduction or delivery for introduction into interstate commerce of a
device that is not in compliance with its conditions of approval is a violation of law.
You are reminded that, as soon as possible and before commercial distribution of your device,
you must submit an amendment to this PMA submission with copies of all approved labeling in
final printed form. Final printed labeling that is identical to the labeling approved in draft form
will not routinely be reviewed by FDA staff when accompanied by a cover letter stating that the
final printed labeling is identical to the labeling approved in draft form. If the final printed
labeling is not identical, any changes from the final draft labeling should be highlighted and
explained in the amendment.
All required documents should be submitted in six copies, unless otherwise specified, to the
address below and should reference the above PMA number to facilitate processing.
U.S. Food and Drug Administration
Center for Devices and Radiological Health
PMA Document Control Center – WO66-G609
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
Page 1 of 4
Page 3 of 4
bearing the applicable PMA reference number, should be submitted to the address below. The
Annual Report should indicate the beginning and ending date of the period covered by the report
and should include the information required by 21 CFR 814.84.
This is a reminder that as of September 24, 2014, class III devices are subject to certain
provisions of the final UDI rule. These provisions include the requirement to provide a UDI on
the device label and packages (21 CFR 801.20), format dates on the device label in accordance
with 21 CFR 801.18, and submit data to the Global Unique Device Identification Database
(GUDID) (21 CFR 830 Subpart E). Additionally, 21 CFR 814.84 (b)(4) requires PMA annual
reports submitted after September 24, 2014, to identify each device identifier currently in use for
the subject device, and the device identifiers for devices that have been discontinued since the
previous periodic report. It is not necessary to identify any device identifier discontinued prior to
December 23, 2013. For more information on these requirements, please see the UDI website,
http://www.fda.gov/udi.
If you have any questions concerning this approval order, please contact Lily Y. Koo, Ph.D. at
301-796-6267.
Sincerely yours,
Erin I. Keith -S
Erin I. Keith, M.S.
Division Director
Division of Anesthesiology, General Hospital,
Respiratory, Infection Control and Dental
Devices
Office of Device Evaluation
Center for Devices and Radiological Health
In addition to the above, and in order to provide continued reasonable assurance of the safety and
effectiveness of the device, the Annual Report must include, separately for each model number
(if applicable), the number of devices sold and distributed during the reporting period, including
those distributed to distributors. The distribution data will serve as a denominator and provide
necessary context for FDA to ascertain the frequency and prevalence of adverse events, as FDA
evaluates the continued safety and effectiveness of the device.
Before making any change affecting the safety or effectiveness of the device, you must submit a
PMA supplement or an alternate submission (30-day notice) in accordance with 21 CFR 814.39.
All PMA supplements and alternate submissions (30-day notice) must comply with the
applicable requirements in 21 CFR 814.39. For more information, please refer to the FDA
guidance document entitled, "Modifications to Devices Subject to Premarket Approval (PMA) The PMA Supplement Decision-Making Process"
(www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm089274
.htm).
You are reminded that many FDA requirements govern the manufacture, distribution, and
marketing of devices. For example, in accordance with the Medical Device Reporting (MDR)
regulation, 21 CFR 803.50 and 21 CFR 803.52, you are required to report adverse events for this
device. Manufacturers of medical devices, including in vitro diagnostic devices, are required to
report to FDA no later than 30 calendar days after the day they receive or otherwise becomes
aware of information, from any source, that reasonably suggests that one of their marketed
devices:
1.
May have caused or contributed to a death or serious injury; or
2.
Has malfunctioned and such device or similar device marketed by the manufacturer
would be likely to cause or contribute to a death or serious injury if the malfunction
were to recur.
Page 2 of 4
Page 4 of 4
5
2. Instructions for Use
A.
Instructions for Use
6.0
POTENTIAL ADVERSE EFFECTS
Below is a list of potential adverse effects (e.g. complications) associated with the device.
Pleural Air Leak Sealant
The PROGEL™ Pleural Air Leak Sealant package is provided sterile.
Caution: Federal (USA) law restricts this device to sale by or on the order of a licensed physician or properly licensed practitioner.
Information for the use of PROGEL™ Pleural Air Leak Sealant is provided in this labeling for Physicians.
Before using PROGEL™ Pleural Air Leak Sealant, please read the following information thoroughly.
1.0
DEVICE DESCRIPTION
PROGEL™ Pleural Air Leak Sealant (PROGEL™ PALS) is a single-use medical device that is formed as a result of mixing two
components: (1) a solution of human serum albumin (HSA) and (2) a synthetic cross-linking component of polyethylene glycol
(PEG) that is functionalized with succinate groups. Upon mixing a clear, exible hydrogel is formed.
PROGEL™ PALS is supplied as a sterile, single-use, 2 component kit which, when mixed makes a 4 ml total sealant volume for
application to visceral pleura as an adjunct to standard visceral pleural closure of visible air leaks incurred during resection of lung
tissue. As PROGEL™ PALS degrades it is metabolized and cleared primarily through the kidneys. Each kit includes:
• One (1) – Chemistry Kit
— One (1) pre-loaded cartridge containing 2 ml of protein solution (processed Human Serum Albumin)
— One (1) pre-loaded cartridge containing polyethylene glycol di-succinimidyl succinate (PEG-(SS)2) as a dried white powder
7.0
Fever/Pyrexia
Fibrillation, Atrial
Dyspnea
Constipation
Nausea
Pneumothorax
Confusion
Hypotension
Anemia
Pain
Subcutaneous Emphysema
Tachycardia
Death
Oliguria
Vomiting
Pneumonia
Pulmonary Inltration
Chest Pain
Pleural Effusion
Urinary Retention
Ileus
•
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Tachycardia, Supraventricular
Abdominal Pain
Arrhythmia
Extrasystoles
Coughing
Hypoxia
Renal Failure, Acute
Adult Respiratory Stress Syndrome
Hyperkalemia
Hyponatraemia
Cardiac Arrest
ECG Abnormal
Renal Function Abnormal
Asthenia
Inuenza-Like Symptoms
Somnolence
Abdomen Enlarged/Distension
Atelectasis
Postoperative Wound Infection
Multiple Organ Failure
Anxiety
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Withdrawal Syndrome
GI Hemorrhage
Hypokalemia
Arrhythmia Atrial
Respiratory Disorder/distress
Respiratory Insufciency
Sepsis
Bronchial Obstruction
Infection Staphylococcal
Pruritus
Delirium/mental status changes
Hypertension
Angina Pectoris
Hemoptysis
Hypoventilation
Pulmonary Air Leakage
Urinary tract infection
Dysuria
Pneumonia Aspiration
Pulmonary haemorrhage
ORIGINAL PIVOTAL CLINICAL STUDY
Study Title: A Randomized Study to Evaluate a Polymeric Patch for Sealing Intraoperative Air Leaks Occurring During Pulmonary
Resection
• One (1) – Applicator Kit
— One (1) 3 ml plastic syringe with 0.5 inch 26 gauge needle
— One (1) 5 ml vial of USP sterile water for injection (2 ml to be used to reconstitute PEG-(SS)2)
7.1
— One (1) applicator assembly with locking push rod
The primary study objective was to evaluate the safety and effectiveness of the use of PROGEL™ Pleural Air Leak Sealant
(PROGEL™ PALS) as an adjunct to standard suture/staple closure of clinically signicant (≥ 2 mm in size) intra-operative visceral
pleural air leaks incurred during open resection of non-infected pulmonary tissue in adults.
— Two (2) spray tips
• One (1) – Instructions for Use (Labeling)
STUDY OBJECTIVES
Optional replacement and extended spray tips are available for convenience and positioning according to surgeon preference:
7.2
PROGEL™ Applicator Spray Tips (pack of 2) REF PGST009, 10 units/box with Instructions
The study was a prospective, “standard care alone” – controlled, 2:1 randomized trial conducted by 5 thoracic surgeon
investigators and 5 sub-investigators at 5 centers in the US. Investigators received detailed device use training, which included
animal model practice; the sub-investigators received basic bench-top training.
PROGEL™ Extended Applicator Spray Tip 16 cm REF PGEN005-06, 4 units/box with Instructions
PROGEL™ Extended Applicator Spray Tip 29 cm REF PGEN005-11, 4 units/box with Instructions
(Sterile Water and Syringe Not Shown)
Enrolled patients were stratied according to pre-operative percent predicted FEV1 (≤ 40%, > 40%). In preparation for open
thoracotomy closure, after evaluation per standard protocol with air leak test and initial attempt to close air leaks (AL) with
standard care (suture/staples), subjects with at least one clinically signicant IOAL (≥ 2 mm in size), were randomized whether
or not to receive PROGEL™ PALS as an adjunct for visceral pleural air leak closure. Investigators conducted an AL test by lling
the chest cavity with warm saline solution or water to submerge the entire lung, simultaneously inating the lung to 20-30 mmHg
(30-40 cm water) and looking for air bubbles, which would represent ALs. The size of each AL was estimated. Any AL ≥ 2 mm
in size was considered clinically signicant. If no leaks or only clinically insignicant leaks (< 2 mm in size) were observed, the
subject was excluded. For enrolled subjects, the size (i.e. < 2 mm, 2-5 mm, and > 5 mm bubbles), location on the lung and source
(e.g. staple line, ssure) of the bubbles coming from ALs were recorded. If a subject had more than 5 leaks, the investigator was
only required to record data on the rst ve air leaks. Up to three attempts to seal AL with the PROGEL™ PALS were permitted.
Locking Push Rod
Protein Solution Cartridge
(Human Serum Albumin)
Applicator Housing
Crosslinker Component Cartridge
(PEG-(SS)2)
Spray Tip
1
2.0
INTENDED USE / INDICATIONS FOR USE
Follow-up through 30 days post-operatively included evaluation of chest x-rays, chest tube air leak, chest tube drainage,
laboratory values, and AEs, as well as time to chest tube removal and patient discharge.
3
Chest tube management was pre-specied as follows:
PROGEL™ Pleural Air Leak Sealant is a single use device intended for application to visceral pleura after standard visceral pleural
closure with, for example, sutures or staples, of visible air leaks incurred during resection of lung parenchyma.
3.0
STUDY DESIGN
Qualifying patients were adults who were undergoing open thoracotomy and willing to use birth control up to 6 weeks post-surgery
and who had intra-operative air leak (≥ 2 mm) following surgery. Patients were excluded if they had a known hypersensitivity to
human albumin, were enrolled in the National Emphysema Treatment Trial or any other study involving tissue sealants, or any
other study not approved by the sponsor. Subjects were also excluded if pregnant and/or breast feeding, if they had signicant
clinical disease that might complicate surgery and/or post-operative recovery and in the investigator’s opinion would complicate
evaluation of device safety and effectiveness.
FIGURE 1. PROGEL™ Pleural Air Leak Sealant Delivery System
CONTRAINDICATIONS
The chest tube will be placed on suction (20-25 cm H2O) for the rst 24 hours. After 24 hours, if there is no air leak, a switch to
water seal will be made. If there is still an air leak after 24 hours the switch will be at the discretion of the surgeon; a record of
what was done will be noted. The chest tube will be removed when:
1. There is no more air leakage following the switch to water seal,
•
Do not use PROGEL™ PALS in patients who have a history of an allergic reaction to Human Serum Albumin or other device
components.
2. The lung has expanded sufciently and/or there is no signicant increase in the size of a pneumothorax, in the investigators’
opinion, that would prevent discontinuation, and
•
Do not use PROGEL™ PALS in patients who may have insufcient renal capacity for clearance of the PROGEL™ PALS
polyethylene glycol load.
3. Drainage has reduced to < 5 cc/kg/24 hours or, 2.5 cc/kg/12 hours.
•
Do not apply PROGEL™ PALS on open or closed defects of main stem or lobar bronchi due to a possible increase in the
incidence of broncho-pleural stulae, including patients undergoing pneumonectomy, any sleeve resection or bronchoplasty.
4.0
5.0
—
STUDY ENDPOINTS
The primary endpoint for PROGEL™ PALS effectiveness was the percent of patients without post- operative air leak (POAL)
through one month post-operatively or the duration of hospitalization, whichever is longer.
Secondary effectiveness endpoints were:
PRECAUTIONS
1. The proportion of intra-operative air leaks (IOAL) in each group that were sealed or reduced, as demonstrated by the air leak
(AL) test, prior to the completion of lung surgery.
• The safety and effectiveness of PROGEL™ PALS has not been established in patients with the following conditions:
—
As to Heimlich Valve use, the protocol stated that ‘occasionally the attending physician will decide to discharge a subject, who
still has an air leak, with a Heimlich valve. When this occurs, the subject will be asked to return on a weekly basis until the tube
is removed. The date the air leak ceased will be the day the tube is removed.’
7.3
WARNINGS
Do not apply PROGEL™ PALS on oxidized regenerated cellulose, absorbable gelatin sponges or any other surface other than
visceral pleura as adherence and intended outcome may be compromised.
Less than 18 years of age, pregnant or nursing women.
2. The proportion of subjects in each group who were free of air leaks immediately following surgery as measured by the presence
of air leaks from the chest tube (CT) at the rst post-operative time point once the subject was in the recovery room (RR).
Contaminated or dirty pulmonary resection cases.
3. The duration of post-operative air leaks measured from the time of surgery until the air leak sealed. For patients discharged
with a Heimlich Valve (HV) for out-patient management of ongoing air leak, air leak duration was the number of days elapsed
from surgery until the subject returned to the clinic with no evidence of an air leak.
—
The presence of an active infection.
—
In the presence of other sealants, hemostatic devices or products other than sutures and staples used in standard
visceral pleural closure.
—
Visceral pleural air leak due to spontaneous pneumothorax, any non-resective pulmonary tissue trauma, or malignancy
as well as congenital or acquired functional or anatomic defect.
—
Patients receiving PROGEL™ PALS in more than one application session (surgery) before and/or after resorption of
PROGEL™ PALS that was applied in any previous surgical session.
Safety was evaluated by assessment of AEs through 30 days post-operatively and changes in the humoral and cellular responses
to PROGEL™ PALS measured pre- and post-surgery.
—
In any area or tissue other than the visceral pleural surface as indicated.
7.4
—
FEV1 ≤ 40% due to small sample size in the clinical study. In the original pivotal study, all 5 PROGEL™ PALS and 4 Control
patients with FEV1 ≤ 40% had post-operative air leak (POAL); whereas in patients with FEV1 > 40%, 59/93 (63.4%)
PROGEL™ PALS and 45/53 (84.9%) Control patients had POAL. See Section 7.9 Effectiveness: Primary Effectiveness
Outcome.
A total of 275 subjects were consented and enrolled and 161 subjects were randomized intra-operatively. Of the 161 randomized
subjects (i.e., 103 PROGEL™ PALS and 58 Control), 148 subjects completed the study. Of the 13 subjects who did not complete
the study (i.e., 1 month follow-up information was not available), 9 died, 1 had a post- PROGEL™ PALS lung transplant, 1 had a
post- PROGEL™ PALS lobectomy of the treated lung, and 2 subjects were lost to follow-up. The pre-treatment-distribution of these
subjects was similar across groups, with 8/103 (7.8%) in the PROGEL™ PALS and 5/58 (8.6%) in the Control groups.
•
Do not use if sterile package and seal are damaged or open, as sterility may be compromised. Do not re-sterilize the contents.
•
PROGEL™ PALS should be refrigerated between 2°C and 8°C (36°F to 46°F). Do not freeze. Store PROGEL™ PALS within the
recommended temperature range. Failure to do so may result in poor product performance. Do not use PROGEL™ PALS after
the expiration date, as sterility or performance may be compromised.
•
Do not use rehydrated cross-linker after 20 minutes, as the performance of PROGEL™ PALS may be compromised.
•
Interruption of the application for approximately 10 seconds may result in occlusion of the spray tip. If occlusion occurs,
remove the spray tip, wipe the end of the applicator to remove any uid, and attach a new spray tip (provided) onto the end of
the applicator.
•
PROGEL™ PALS is intended for single use only. Do not re-sterilize or reuse any component.
•
PROGEL™ PALS use with any additive (e.g. antibiotics) to any component has not been studied.
•
Discard unused material in accordance to standard practice for PROGEL™ PALS components.
•
PROGEL™ PALS resorption time in humans has not been studied. In rats, over 50% of a 14C-labeled device was excreted after
24 hours and virtually all radioactivity was recovered from rats at 14 days post-implant. The PROGEL™ PALS was also largely
absent at 4 days with only isolated fragments of the PROGEL™ PALS apparent at 7 days after implantation on pigs’ lungs.
•
Human Serum Albumin - HSA (USP) in the PROGEL™ PALS kit is obtained from an FDA licensed supplier and the protein
is derived from plasma collected from donors who have been screened and tested according to the methods specied by
the FDA. These methods minimize the possibility that drawn blood will contain communicable diseases or viruses such as
hepatitis and HIV.
•
Do not use more than 30 ml of PROGEL™ PALS per patient.
2
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4. The duration of chest tube placement. This endpoint included the time that the Heimlich Valve was in place.
5. The duration of hospitalization: post-operative hospital days (POD).
SUBJECT ACCOUNTING
4
7.5
DEMOGRAPHICS
7.7
The demographics of the subjects enrolled in the study are presented in Table 1.
TABLE 1. Patient Demographics
N
Gender:
Age, years:
Percent predicted FEV1:
Immunosuppression:
Diabetes:
COPD:
Previous Thoracic Surgery:
Radiation Exposure – Chest:
Chemotherapy:
Steroid Use:
Smoking:
Male
Female
Mean
SD
≤ 40%
> 40%
Missing
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
Never
Current
Former
PROGEL™ PALS
103
66 (64.1%)
37 (35.9%)
63.6
13.6
5 (4.9%)
93 (90.3%)
5 (4.9%)
98 (95.1%)
5 (4.9%)
90 (87.4%)
13 (12.6%)
68 (66.0%)
35 (34.0%)
88 (85.4%)
15 (14.6%)
94 (91.3%)
9 (8.7%)
94 (91.3%)
9 (8.7%)
99 (96.1%)
4 (3.9%)
20 (19.4%)
18 (17.5%)
65 (63.1%)
Control
58
36 (62.1%)
22 (37.9%)
65.9
11.1
4 (6.9%)
53 (91.4%)
1 (1.7%)
55 (94.8%)
3 (5.2%)
51 (87.9%)
7 (12.1%)
42 (72.4%)
16 (27.6%)
48 (82.8%)
10 (17.2%)
53 (91.4%)
5 (8.6%)
56 (96.6%)
2 (3.4%)
55 (94.8%)
3 (5.2%)
11 (19.0%)
11 (19.0%)
36 (62.1%)
78
59.8 ± 36.0
50.0
1
175
40 (38.8%)
5 (4.9%)
11 (10.7%)
21 (20.4%)
13 (12.6%)
7 (6.8%)
13 (12.6%)
4 (3.9%)
35 (34.0%)
15 (14.6%)
9 (8.7%)
9 (8.7%)
4 (3.9%)
13 (12.6%)
46
47.6 ± 27.3
40.5
1
120
26 (44.8%)
3 (5.2%)
10 (17.2%)
19 (32.8%)
5 (8.6%)
5 (8.6%)
7 (12.1%)
3 (5.2%)
16 (27.6%)
10 (17.2%)
5 (8.6%)
2 (3.4%)
3 (5.2%)
9 (15.5%)
82 (79.6%)
6 (5.8%)
15 (14.6%)
36 (35.0%)
44 (75.9%)
7 (12.1%)
7 (12.1%)
25 (43.1%)
72 (69.9%)
23 (22.3%)
2 (1.9%)
0 (0%)
1 (1.0%)
5 (4.9%)
38 (65.5%)
18 (31.0%)
0 (0.0%)
0 (0%)
0 (0.0%)
2 (3.4%)
NUMBER OF PROGEL™ PALS APPLICATIONS
2 ml of PROGEL™ PALS was expected to cover a 20 cm2 (3 in2) surface area with 1 mm thickness of PROGEL™ PALS, which was
expected to be sufcient to treat an average clinically signicant visceral pleural AL. Up to three applications of PROGEL™ PALS
were allowed per individual air leak. Table 3 reports the actual number of PROGEL™ PALS applications as well as the number of
2 ml PROGEL™ PALS units used per patient.
TABLE 3. Volume of PROGEL™ Pleural Air Leak Sealant Used
Pack Years
N
Mean ± SD
Median
Minimum
Maximum
Hypertension
Immunosuppression
History of Myocardial Infarction
Coronary Artery Disease
Renal Disease
History of Neurological Event
Diabetes
Congestive Heart Failure
Chronic Obstructive Pulmonary Disease
Previous Thoracic Surgery
Radiation Exposure-Chest
Chemotherapy
Steroid Use
Recent Weight Loss
Alcohol Dependency
No
Current
Past
Prior Cancer
ECOG Score
0 = Fully active
1 = Ambulatory
2 = In bed <50%
3 = In bed >50%
4 = Bedridden
Missing
Volume of PROGEL™ PALS Used per Patient (ml)
2
4
6
8
10
12
18
30
Mean ± SD
Median
Minimum
Maximum
29 (28.2%)
37 (35.9%)
22 (21.4%)
7 (6.8%)
4 (3.9%)
2 (1.9%)
1 (1.0%)
1 (1.0%)
4.8 ± 3.6
4.0
2
30
Number of PROGEL™ PALS Applications per AL
1
2
3
Missing/Other
PROGEL™ PALS - N (%)
125 (59.5)
70 (33.3)
9 (4.3)
6 (2.9)
Time (minutes) of Application / Unit
Mean ± SD
Median
Minimum
Maximum
3.3 ± 4.7
2.0
1
-
Total Application Time (minutes)
Mean ± SD
Median
Minimum
Maximum
7.9 ± 8.4
6.0
1
63
Table 4 provides additional information on patient surgeries.
TABLE 4. Other Operative Details
Treatment
No. of Chest Tubes
Time in OR (min)
Time to Skin Closure (min)
1
2
≥3
N
Mean ± SD
Median
Minimum
Maximum
N
Mean ± SD
Median
Minimum
Maximum
PROGEL™ PALS
19 (18.4%)
83 (80.6%)
1 (1.0%)
102
226.7 ± 61.2
225.5
115
455
91
156.8 ± 54.9
151.0
52
355
Control
7 (12.1%)
48 (82.8%)
3 (5.2%)
58
236.8 ± 61.5
225.5
145
430
50
165.0 ± 62.6
143.5
81
387
None of the differences between PROGEL™ PALS and Control groups for the reported demographic and risk variables was found
to be statistically signicant per Wilcoxon Rank Sum Test. The enrollment of patients with percent predicted FEV1 ≤ 40% was less
than 6% of each cohort limiting clinical assessment of outcomes for this cohort. There were no clinically notable or statistically
signicant differences in pre-operative pulmonary function test results.
5
7.6
PRIMARY DIAGNOSIS AND PROCEDURE VARIABLES
7.8
Table 2 presents a summary of primary diagnoses, type of surgery, surgical approach, extent of lymphadenectomy, intraoperative air leak (IOAL) distribution and extent of pleural adhesions.
PROGEL™ PALS
103
Control
58
70 (68.0%)
19 (18.4%)
6 (5.8%)
3 (2.9%)
5 (4.9%)
42 (72.4%)
8 (13.8%)
3 (5.2%)
0 (0.0%)
5 (8.6%)
4 (3.9%)
55 (53.4%)
5 (4.9%)
12 (11.7%)
8 (7.8%)
10 (9.7%)
5 (4.9%)
1 (1.0%)
3 (2.9%)
1 (1.7%)
34 (58.6%)
4 (6.9%)
7 (12.1%)
2 (3.4%)
5 (8.6%)
2 (3.4%)
1 (1.7%)
2 (3.4%)
1 (1.0%)
85 (82.5%)
3 (2.9%)
13 (12.6%)
1 (1.0%)
1 (1.7%)
45 (77.6%)
6 (10.3%)
6 (10.3%)
0 (0.0%)
30 (29.1%)
30 (29.1%)
43 (41.7%)
11 (19.3%)
14 (24.6%)
32 (56.1%)
1 (1.0%)
49 (47.6%)
53 (51.5%)
3 (5.7%)
28 (52.8%)
22 (41.5%)
1 (1.7%)
27 (46.6%)
30 (51.7%)
1 (3.3%)
14 (46.7%)
15 (50.0%)
33 (32.0%)
46 (44.7%)
16 (15.5%)
2 (1.9%)
4 (3.9%)
2 (1.9%)
30 (51.7%)
14 (24.1%)
6 (10.3%)
5 (8.6%)
0 (0.0%)
3 (5.2%)
3.0
9.7
2.0
1
100
2.0
1.4
1.0
1
7
ADVERSE EVENTS (AEs)
Table 5 presents the incidence of adverse events (AEs) reported for greater than 1% of subjects in either treatment group during
a clinical study in 161 subjects randomized in a 2:1 ratio (i.e. 103 PROGEL™ PALS and 58 Control patients).
TABLE 5. Incidence of AEs Reported by > 1% of Subjects by Treatment Group*
TABLE 2. Primary Diagnosis and Procedure Variables
N
Primary Diagnosis, p = 0.620
Primary Tumor
Metastatic Tumor
Benign Tumor
COPD/Bronchitis/Emphysema
Other
Type of Surgery, p = 0.883
Bilobectomy
Lobectomy
Segmentectomy
Single Wedge
Multiple Wedge
Lobectomy with Wedge(s)
Lobectomy/Segment/Other
Lung Volume Reduction
Other
Surgical Approach, p = 0.269
Median Sternotomy
Posterolateral Thoracotomy
Anterolateral Thoracotomy
Mini-thoracotomy
Other
Lymphadenectomy, p = 0.201
Not done
Partial
Complete
Pleural Adhesions, p = 0.597
Missing
No
Yes
Unspecied
Minimal
Extensive
IOAL prior to closure
actual distribution, p = 0.0051
1
2
3
4
5
>5
IOAL statistical distribution, p = 0.134
Mean
SD
Median
Minimum
Maximum
7
Preferred Term
Fever
Dyspnea
Constipation
Nausea
Pneumothorax
Confusion
Hypotension
Anemia
Pain
Tachycardia
Death
Oliguria
Vomiting
Pneumonia
Chest Pain
Pleural Effusion
Urinary Retention
Ileus
Abdominal Pain
Arrhythmia
Extrasystoles
Coughing
Hypoxia
Hyperkalaemia
Hyponatraemia
Cardiac Arrest
ECG Abnormal
Asthenia
Somnolence
Abdomen Enlarged
PROGEL™ PALS
N=103
22 (21.4%)
12 (11.7%)
12 (11.7%)
11 (10.7%)
10 (9.7%)
9 (7.8%)
8 (7.8%)
8 (7.8%)
8 (7.8%)
7 (6.8%)
7 (6.8%)
7 (6.8%)
5 (4.9%)
5 (4.9%)
5 (4.9%)
5 (4.9%)
4 (3.9%)
4 (3.9%)
4 (3.9%)
3 (2.9%)
3 (2.9%)
3 (2.9%)
3 (2.9%)
3 (2.9%)
3 (2.9%)
3 (2.9%)
3 (2.9%)
3 (2.9%)
3 (2.9%)
2 (1.9%)
2 (1.9%)
2 (1.9%)
2 (1.9%)
2 (1.9%)
2 (1.9%)
2 (1.9%)
2 (1.9%)
2 (1.9%)
Control
N=58
12 (20.7%)
7 (12.1%)
10 (17.2%)
6 (10.3%)
7 (12.1%)
5 (8.6%)
5 (8.6%)
6 (10.3%)
6 (10.3%)
4 (6.9%)
5 (8.6%)
6 (10.3%)
4 (6.9%)
1 (1.7%)
7 (12.1%)
7 (12.1%)
0 (0.0%)
1 (1.7%)
3 (5.2%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
1 (1.7%)
1 (1.7%)
Preferred Term
Atelectasis
Anxiety
Withdrawal Syndrome
GI Haemorrhage
Hypokalaemia
Arrhythmia Atrial
Respiratory Disorder
Sepsis
Pruritus
Delirium
Hypertension
Angina Pectoris
Hemoptysis
Arthropathy
Gall Bladder Disorder
Cachexia
Dehydration
Non-protein Nitrogen Increased
Edema Dependent
Edema Generalized
Fibrillation Ventricular
Cardiac Failure
Hypoventilation
Thrombocytopenia
Allergic Reaction
Fatigue
Rigors
Infection, Fungal
Healing, Impaired
Cramps, Legs
Acidosis, Respiratory
Chyle, Leak
PROGEL™ PALS
N=103
2 (1.9%)
2 (1.9%)
2 (1.9%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
Control
N=58
2 (3.4%)
2 (3.4%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
2 (3.4%)
2 (3.4%)
2 (3.4%)
2 (3.4%)
3 (5.2%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
1 (1.7%)
*There were no statistically signicant differences (p > 0.05) in the incidence of AEs between the PROGEL™ PALS and Control groups.
ADVERSE EVENTS
Table 6 presents those AEs considered by the investigator to be possibly or probably related to the PROGEL™ PALS. There
were 3 subjects in the PROGEL™ PALS group with AEs that were considered by the investigator to be possibly or probably
related to the device. The AEs reported were: chest pain, constipation, gastroesophageal reux, nausea, cough, dyspnea,
pneumothorax, and subcutaneous emphysema. All were reported as a single occurrence in the PROGEL™ PALS group.
Two of the AEs, dyspnea and chest pain, were reported as “severe” and “serious”, respectively and occurred in the same
subject. All others were reported as mild or moderate.
The most frequent type of surgery was lobectomy for both groups. In both the PROGEL™ PALS and Control groups, the
posterolateral thoracotomy was the most frequently used surgical approach for open thoracotomy. Intra-operative characteristics
were similar between the PROGEL™ PALS and Control groups for the individual parameters evaluated. Data indicates that the
baseline distribution of IOAL was statistically different between treatment groups (p=0.0051); the mean and median were not.
Other variables were not statistically different as powered in this study.
6
TABLE 6. Incidence of Adverse Events in PROGEL™ PALS Group
Considered Possibly or Probably Device Related
Body System
Preferred Term
Body as a Whole
PROGEL™ PALS
N=103
Chest Pain
Gastrointestinal Systems
Constipation
Gastroesophageal Reux
Nausea
Respiratory System
Coughing
Dyspnea
Pneumothorax
Skin and Appendages
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
1 (1.0%)
8
7
A.
(cont.)
(cont.)
UNANTICIPATED ADVERSE DEVICE EVENT
A large, symptomatic pneumothorax that occurred in a 28 year old PROGEL™ PALS-treated subject at three weeks post open
pulmonary metastectomy and required chest tube placement was considered by the investigator to be an unanticipated
adverse device effect due to the temporal relationship of the event with the use of PROGEL™ PALS. No other unanticipated
adverse events were reported.
OTHER SERIOUS ADVERSE EVENTS
Table 7 presents a summary of other serious adverse events (SAEs). There were 5 other SAEs: 2 in the PROGEL™ PALS
group and 3 in the Control group. Both of the PROGEL™ PALS SAEs were considered by the investigator probably not related
to the device. All of the events resulted in extended hospital stays or rehospitalization; 4 subjects recovered from these
events and 1 subject continued on dialysis.
TABLE 7. Other Serious Adverse Events
Subject ID
PROGEL™ PALS
03-02-201
03-01-211
Control
01-01-204
02-02-206
03-01-219
Age/Gender
Relationship To Device
Event
Probably Not Related
Acute Renal Failure
Myocardial Infarction
Continues on Dialysis
Recovered
83 / Male
67 / Female
70 / Male
Not Related
Not Related
Fluid/Air in Lung & GI Bleed
ARDS
Dehydration
Recovered
Recovered
Recovered
a
Control
58
5 (8.6%)
1 (1.7%)
Recovery Room
a
Control
Control
Acute renal failure*
Oliguria
15
12
*Pre-existing renal disease
***no discharge or 1MFU as patient died
***
11****
1.0
1.2
Control
53
0
1 (1.7%)
1 (1.7%)
10
9/95 (9.5%)
2
2/53 (3.8%)
PROGEL™ PALS
ml used
6
4
2
2
6
4
8
6
2
Severe
Severe
Severe
Severe
Severe
Moderate
Moderate
Mild
Mild
na
na
Severe
Mild
***
1.0****
Post-op
Control
2 (1.9%)
54 (52.4%)
18 (17.5%)
7 (6.8%)
6 (5.8%)
3 (2.9%)
13 (12.6%)
2 (3.4%)
29 (50.0%)
14 (24.1%)
6 (10.3%)
1 (1.7%)
3 (5.2%)
3 (5.2%)
4.7
6.8
2.0
0.5
42
101
3.6
3.9
2.0
0.5
22
56
11
As to stratication for pre-op FEV1 ≤ or > 40%, mean (median) air leak duration for patients with FEV1 ≤ 40% was 6.3 (4.0)
days for PROGEL™ PALS and 4.3 (3.0) days for Control subjects; for patients with FEV1 > 40% the mean (median) air leak
duration was 4.7 (2.0) days for PROGEL™ PALS and 3.6 (2.0) days for the Control cohorts.
FIGURE 2. Air leak Free and Recurrence of Air Leak by Post-Operative Days (POD)
100
90
AL-free
80
70
Sealant AL-free
Control AL-free
Sealant RAL
Control RAL
60
50
40
30
20
10
0
TABLE 10. Summary of Subject Deaths
RAL
2
4
6
8 10 12 14 16 18 20 22 24 26 28 30
POD
Amount of
PROGEL™ PALS Used
Note: For all patients (N = 161), including those discharged home with Heimlich Valve.
Recurrence of air leak (RAL) is dened as chest tube documented air leak following one or more air- leak free days. One
PROGEL™ PALS patient experienced a late pneumothorax on POD25 was also counted as having a recurrence of air leak.
Overall, data demonstrates that the duration of POALs was comparable for both treatment groups with a majority of POALs
lasting less than three days: median duration was two days in both groups. For each post-operative day, patients were
excluded from the analysis if they were dead, lost to follow-up, had no air-leak assessment, received lung transplant, or
completed 1MFU. Patients who were discharged with a Heimlich Valve were counted as having AL on the post-operative
days between the date of discharge and the date of chest tube removal.
PROGEL™ PALS
71/Male
ECOG = 4, FEV1 ≤ 40%
POD2
Not Related
ARDS
30 ml
82/Male
ECOG = 0, FEV1 > 40
POD28
Not Related
Pneumonia
4 ml
61/Male
ECOG = 1, FEV1 > 40
POD10
Not Related
Acute Airway Obstruction or
Pulmonary Embolism
2 ml
66/Male
ECOG = 1, FEV1 > 40
POD6
Not Related
ARDS & Multisystem Failure
6 ml
65/Male
ECOG = 2, FEV1 > 40
POD22
Not Related
ARDS & Multisystem Failure
4 ml
80/Female
ECOG = 0, FEV1 > 40
POD19
Not Related
Pneumonia
N/A
70/Male
ECOG = 1, FEV1 > 40
POD22
Not Related
Atrial Fibrillation
N/A
82/Male
ECOG = 0, FEV1 > 40
POD0
Not Related
Ventricular Fibrillation
N/A
67/Male
ECOG = unknown, FEV1 > 40
POD38
Not Related
Anoxic Brain Injury
N/A
Table 15 presents a summary of the duration of chest tube placement in number of post-operative days. The duration of
chest tube placement was comparable for both treatment groups. The median duration of CT placement for both groups
was ve days.
Control
TABLE 15. Duration of CT Placementa
CT Duration
N
Missingb
N
0-2 days
3-4 days
5-6 days
7-9 days
10-11 days
> 11 days
EFFECTIVENESS
PRIMARY EFFECTIVENESS OUTCOME
Percentage of subjects who remained air leak-free through the 1 MFU visit is presented in Table 11.
TABLE 11. Primary Endpoint Results
Air Leak Status Through 1MFU Visit
No POAL
With POAL
PROGEL™ PALS N (%)
36 (35.0%)
67 (65.0%)
Control N (%)
8 (13.8%)
50 (86.2%)
P-valuea
a
0.005
Mean
SD
Median
Minimum
Maximum
103
3 (2.9%)
100
2 (1.9%)
34 (33.0%)
37 (35.9%)
11 (10.7%)
3 (2.9%)
13 (12.6%)
6.8
5.5
5.0
2
42
Control N (%)
58
3 (5.2%)
55
0 (0.0%)
19 (32.8%)
21 (36.2%)
9 (15.5%)
3 (5.2%)
3 (5.2%)
6.2
3.5
5.0
3
22
Differences were not statistically signicant as determined by a Wilcoxon Rank Sum Test
comparing PROGEL™ PALS and Control groups based on all available data (N = 155).
“Missing” subjects were either censored (incomplete, i.e., entered the study late and didn’t have a chance
to complete the whole study, lost-to-follow-up, or other causes). The time-to-event survival analyses included all subjects
into the analyses and used all subject information up to the time they were censored.
b
Logistic regression analysis comparing PROGEL™ PALS and Control groups for the primary endpoint analysis.
As to stratication for pre-op FEV1 ≤ or > 40%, all 5 PROGEL™ PALS and 4 Control patients with FEV1 ≤ 40% had POAL;
whereas 59/93 (63.4%) PROGEL™ PALS and 45/53 (84.9%) Control patients with FEV1 > 40% had POAL.
SECONDARY EFFECTIVENESS OUTCOMES
Proportion of intra-operative air leaks (IOAL) in each group that were sealed or reduced, as demonstrated by the air leak
(AL) test, prior to the completion of lung surgery is presented in Table 12. Of the 210 ALs tracked in the PROGEL™ PALS
group, 76.7% were sealed after the application of PROGEL™ PALS compared with 15.7% of the 108 ALs in the Control group.
IOALs were sealed in 70.9% of the PROGEL™ PALS and 10.3% of the Control subjects following the nal AL test.
10
8
PROGEL™ PALS
9
The single patient who received the maximum volume of PROGEL™ PALS used in this clinical trial (15 Units, or 30 ml total
volume) was a 71 year old male who, about ve days after bilateral lung volume reduction surgery, developed signicant
ALs that were repaired with PROGEL™ PALS application. ARDS was noted 0-6 hours post-op PROGEL™ PALS application.
The patient developed pulseless ventricular brillation and utter and died on POD 2 after PROGEL™ PALS application;
autopsy ndings bilaterally included moderate pleural cavity adhesions on gross exam, congestion on cut lung surface, and
brinous pleuritis microscopically.
a
0.002
It is clinically notable that ten (10%) subjects in the PROGEL™ PALS group and one (2%) subject in the Control group were
discharged from the hospital with a Heimlich Valve (the difference was not statistically signicant as powered in this study).
Since patients discharged with a HV valve were re-evaluated weekly rather than daily, patient discharge from the hospital
with a HV confounded determination of the true duration of post-operative air-leaks, which may in part explain the higher
proportion of PROGEL™ PALS patients with air leak that continues through more than 11 days.
Table 10 presents a summary of subject deaths. 5/103 (4.9%) PROGEL™ PALS and 4/58 (6.9%) control subjects died during
this study. None of the deaths were considered by the investigators to be device- related. Death in 2 PROGEL™ PALS and
1 control patient was associated with multi-organ failure. 1 control treated patient reported to have multi-organ failure was
not reported to have died. Death in 2 of 3 PROGEL™ PALS patients with ARDS was associated with more than the mean
(2.5 Units = 5 ml) and median (2.0 Units = 4 ml) amount of PROGEL™ PALS used in clinical study.
7.9
P-valuea
*Differences were not statistically signicant as determined by a Wilcoxon Rank Sum Test
comparing PROGEL™ PALS and Control groups based on all available data (N=157).
SUBJECT DEATHS
Cause of Death
Control N (%)
19 (32.8%)
20 (34.5%)
16 (27.6%)
3 (5.2%)
0 (0.0%)
Data demonstrate that overall the mean duration of post-operative air leaks was 1.1 days longer for the PROGEL™ PALS
cohort than the control cohort, with no difference in the median duration (2 days in each cohort). Data also indicate that
while 2.4% more PROGEL™ PALS patients had no air leak at 0-2 days, 10.1% more control patients had no air leak at 3-6
days, and that 7.4% more PROGEL™ PALS patients’ air leak continued through more than 11 days.
Urinary system disorders occurred in 12 patients in the PROGEL™ PALS group (11.7%), and 2 patients in the Control group
(3.4%). Reasons for the difference between cohorts in the incidence of renal AEs are unclear; the potential of PROGEL™
PALS to exacerbate renal dysfunction in patients with pre-existing renal disease is unknown.
Relationship to Device
< 0.001
P-value associated with Fisher’s Exact Test of categorical data.
Duration POAL
N (%)
Missing
0 - 2 days
3 - 4 days
5 - 6 days
7 - 9 days
10 - 11 days
> 11 days
Severity
**at discharge; no 1MFU as patient died
****at discharge; no 1MFU data
Day of Death
56 (54.4%)
30 (29.1%)
7 (6.8%)
8 (7.8%)
2 (1.9%)
Mean
SD
Median
Minimum
Maximum
N
Data demonstrated pre-existing renal disease in 3 PROGEL™ PALS and 1 control patients who had a renal AE, and no
pre-existing renal disease in 6 PROGEL™ PALS and 1 control patients who had a renal AE. Severe renal AEs occurred in 4
PROGEL™ PALS patients without pre-existing disease and 2 of those patients died. Severe renal AE occurred in 1 control
device patient with pre-existing disease and that patient died.
Age , Gender
Pre-op ECOG Score,
Pre-op FEV1 ≤ or > 40%
< 0.001
TABLE 14. Duration of Post-Operative Air Leaks*
PROGEL™ PALS
95
2 (1.9%)
3 (2.9%)
5 (4.9%)
Creatinine
Pre-op
1 MFU
1.1
1.8
0.7
1.8**
1.4
1.7
3.8
5.0
1.0
***
1.1
1.3
1.7
2.2
0.9
1.0
0.9
0.8
P-valuea
Duration of post-operative air leaks measured from the time of surgery until the air leak sealed. For patients discharged
with a Heimlich Valve (HV) for out-patient management of an ongoing air leak, air leak duration was the number of days
elapsed from surgery until the subject returned to the clinic with no evidence of an air leak. Duration of POAL was dened
as the rst post-operative day (POD) on which the AL was noted. Time to no air leak is presented in Table 14.
TABLE 9. Incidence of Adverse Events Related to Renal Function (n, %)
Subjects with Renal Function (RF) Adverse Events
Treatment
Adverse Event
BUN
Pre-op
1 MFU
PROGEL™ PALS
Abnormal RF
25
26
Abnormal RF, oliguria
23
84**
PROGEL™ PALS
PROGEL™ PALS
Acute renal failure
21
24
PROGEL™ PALS
Acute renal failure*
54
14
Acute renal failure
8
***
PROGEL™ PALS
PROGEL™ PALS
Oliguria*
13
17
PROGEL™ PALS
Oliguria*
33
39
Oliguria
12
8
PROGEL™ PALS
PROGEL™ PALS
Oliguria
10
11
Control N (%)
17 (15.7%)
13 (12.0%)
60 (55.6%)
17 (15.7%)
1 (0.9%)
6 (10.3%)
51 (87.9%)
1 (1.7%)
P-value associated with Fisher’s Exact Test for categorical data.
Response
No AL
Occasional Infrequent Bubbles
Frequent Bubbles
Continuous Bubbles
Missing
RENAL EVENTS
PROGEL™ PALS degradation products are primarily cleared from the body by the kidneys. The incidence of Renal AEs along
with individual subject data are in Table 9.
Renal Adverse Events
N, patients through 1MFU
Abnormal renal function
Acute renal failure
Oliguria
Total number of renal adverse events*
% patients with renal adverse events
*1 PROGEL™ PALS patient was reported to have 2 events: abnormal renal function and oliguria
161 (76.7%)
23 (11.0%)
21 (10.0%)
5 (2.4%)
0 (0.0%)
73 (70.9%)
30 (29.1%)
0 (0.0%)
TABLE 13. Summary of POALs in the Recovery Room
TABLE 8. Pleural Air Leak and Air Space Events
PROGEL™ PALS
102
9 (8.7%)
3 (2.9%)
Sealed IOAL/Subject
Observation Period
PLEURAL AIR LEAK AND AIR SPACE EVENTS
PROGEL™ PALS is a HSA – PEG polymer hydrogel applied to visceral pleura and is substantially resorbed within the rst
week after such application. Upon lung expansion, the PROGEL™ PALS interposes between visceral and parietal pleura. It
is unknown if interpleural PROGEL™ PALS changes post-operative visceral and parietal pleura surface adhesion, changes
surface healing and allows air leak sites to re-open upon PROGEL™ PALS resorption. Data demonstrated that pneumothorax
occurred in 8.7% of the patients and 8.6% of the control patients. In addition ARDS occurred in 2.9% PROGEL™ PALS
compared to 1.7% control patients; PROGEL™ PALS patients with ARDS died. Event incidences are in Table 8.
Pleural Air Leak and Air Space Events
N
Pneumothorax as an adverse event
Acute Respiratory Distress Syndrome
Response
No IOAL
< 2 mm
2-5 mm
> 5 mm
Missing
No IOALs
With IOALs
Missing
Proportion of subjects in each group who were free of air leaks immediately following surgery as measured by the presence
of air leaks from the chest tube (CT) at the rst post-operative time point once the subject was in the recovery room (RR) is
presented in Table 13. After surgery, subjects were transferred to the recovery room where chest tubes (CTs) were placed
on suction and the subjects’ air leakage was determined by observing air bubbles in the CT drainage system. A statistically
signicant number of PROGEL™ PALS subjects were air leak-free in recovery room compared to Control subjects. No ALs
were observed in the recovery room in 54% of the PROGEL™ PALS and 33% of the Control subjects.
Outcome
70 / Female
70 / Male
TABLE 12. IOAL Closure Summary
Parameter
Sealed IOAL/Individual AL
Consistent results were observed using a survival analysis, which included all randomized patients (N=161) and treated
patients with missing time of CT removal as censored observations. The results of the survival analysis are shown in Figure
3 below.
As to stratication for pre-op FEV1 ≤ or > 40%, mean (median) chest tube placement duration for patients with FEV1 ≤
40% was 8.3 (7.0) days for PROGEL™ PALS and 5.8 (4.5) days for Control subjects; for patients with FEV1 > 40%, the mean
(median) chest tube placement duration was 6.8 (5.0) days for PROGEL™ PALS and 6.2 (5.5) days for the Control cohorts.
12
FIGURE 3. Time to Chest Tube (CT) Removal
TABLE 17. Patient Demographics
1.0
Total
(N=112)
112
0.8
N
Gender
Male
Female
Race
Asian
Other
Black or African-American
White
Age
Mean
SD
Median
Minimum
Maximum
Age Category
< 65
≥ 65
Medical Risk Factors
0.6
0.4
0.2
0.0
2
4
6
Group
N
Sealant
103
5
6.97
Control
58
Median
5
Mean
6.71
log-rank p
0.896
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42
TIme in Days
Sealant
Control
NOTE: For all patients (N = 161), including those discharged home with Heimlich Valve
Table 16 presents the duration of hospitalization or post-operative hospital days (POD).
TABLE 16. Duration of Hospitalization POD
Hospital Stay, Days
N
Missingb
N
3-4 days
5-6 days
7-9 days
10-11 days
> 11 days
103
5 (4.9%)
98
11 (10.7%)
49 (47.6%)
22 (21.4%)
7 (6.8%)
9 (8.7%)
7.44
3.4
6.0
3
23
Mean
SD
Median
Minimum
Maximum
a
Control N (%)
58
3 (5.2%)
55
4 (6.9%)
23 (39.7%)
16 (27.6%)
5 (8.6%)
7 (12.1%)
9.35
5.6
7.0
4
38
P-Valuea
0.0413
Pre-Specied Risk Factors
Hypertension
Diabetes
If Diabetes: Insulin
If Diabetes: Oral agents
Immunosuppression (yes)
Renal Disease (yes)
History of Myocardial Infarction
Cardiovascular Disease (yes)
History of Stroke
History of Transient Ischemic Attack
Congestive Heart Failure
If Congestive Heart Failure: Class I
COPD (yes)
Cancer History (yes)
Previous Thoracic Surgery (yes)
Previous Therapeutic Radiation to Thorax (yes)
Current Systemic Chemotherapy (yes)
Pre-operative Use of Steroids
Weight Loss of ≥ 10 lbs in Last Year (yes)
Alcohol Abuse
If Alcohol Abuse: Current
If Alcohol Abuse: Past
Cigarette Smoking
If Cigarette Smoking: Current
If Cigarette Smoking: Past
Drug Abuse
If Drug Abuse: Past
Other Signicant Medical History (yes)
P-value associated with Wilcoxon Rank Sum Test comparing PROGEL™ PALS and Control groups based on all available data (N = 155).
b
“Missing” subjects were either censored (incomplete, i.e., entered the study late and didn’t have a chance
to complete the whole study, lost-to-follow-up, or other causes). The time-to-event survival analyses included all subjects
into the analyses and used all subject information up to the time they were censored.
Consistent results were observed using a survival analysis, which included all randomized patients (N = 161) and treated
patients with missing time of hospital discharge as censored observations. The results of the survival analysis are shown
in Figure 4.
FIGURE 4: Time to Hospital Discharge
1.0
0.8
0.6
0.4
0.2
0.0
2
4
6
Group
N
Sealant
103
6
7.44
Control
58
Median
7
Mean
9.35
log-rank p
0.413
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38
Time in Days
Sealant
Control
NOTE: For all patients (N = 161), including those discharged home with Heimlich Valve
46 (41.1%)
66 (58.9%)
3 (2.7)
1 (0.9)
3 (2.7)
105 (93.8)
67.1
11.21
69
34
87
39 (34.8%)
73 (65.2%)
Total
N=112
64 (57.1%)
17 (15.2%)
4 (3.6%)
10 (8.9%)
2 (1.8%)
10 (8.9%)
7 (6.3%)
37 (33.0%)
4 (3.6%)
4 (3.6%)
5 (4.5%)
1 (0.9%)
34 (30.4%)
58 (51.8%)
2 (1.8%)
6 (5.4%)
3 (2.7%)
17 (15.2%)
10 (8.9%)
11 (9.8%)
6 (5.4%)
5 (4.5%)
81 (72.3%)
21 (18.8%)
60 (53.6%)
1 (0.9%)
2 (1.8%)
77 (68.8%)
13
15
7.10 OTHER SAFETY ASSESSMENT
TABLE 18. Primary Diagnosis and Procedural Characteristics
HUMORAL AND CELL-MEDIATED IMMUNE RESPONSE
Primary Diagnosis (post-operatively)
N
112
Primary Tumor
87 (77.7%)
Metastatic tumor
11 (9.8%)
Benign tumor
4 (3.6%)
COPD
3 (2.7%)
Chronic bronchitis
1 (0.9%)
Emphysema
0 (0.0%)
Other
11 (9.8%)
Operative Procedure*
Bilobectomy
6 (5.4%)
Lobectomy
61 (54.5%)
Segmentectomy
15 (13.4%)
Wedge Resection
35 (31.3%)
Decortication
2 (1.8%)
Biopsy
5 (4.5%)
Surgery Type
Video-Assisted
40 (35.7%)
Robotic-Assisted
72 (64.3%)
Time in OR (mins)
Mean
225.4
SD
66.25
Median
214.5
Minimum
79
Maximum
433
Time to skin closure (mins)
Mean
155.4
SD
61.26
Median
143.0
Minimum
47
Maximum
401
IOAL prior to closure
1
91 (81.3%)
2
20 (17.9%)
3
1 (0.9%)
IOAL size prior to closure
< 2mm
40/133 (30.1%)
2-5mm
88/133 (66.2%)
> 5mm
5/133 (3.8%)
Both pre- and post-operative serum samples were obtained from 71/103 (69%) PROGEL™ PALS and 37/58 (64%) Control
subjects. Seventy (70) of the PROGEL™ PALS and 36 of the Control subjects showed no immune reaction to the PROGEL™
PALS. One (1) subject in each group had pre-operative and post-operative serum levels consistent with the presence of
PROGEL™ PALS antibodies prior to device exposure.
The response of peripheral blood mononuclear cells to various concentrations of mitogens (i.e. Con A, PHA, and PWM),
recall antigens (Candida and Tetanus), and PROGEL™ PALS was tested by mixed lymphocyte proliferative assay (LPA) in
pre- and post-operative whole blood samples. Mitogen analyses were compared in pre- and post-operative samples of 59
PROGEL™ PALS and 34 Control subjects and recall antigen and PROGEL™ PALS analyses were performed in 69 PROGEL™
PALS and 32 Control subjects. No clinically signicant differences were observed in the pre- and post-operative blood
samples for either Control or PROGEL™ PALS subjects.
8.0
RESULTS OF THE VATS/ROBOTICS SUPPORTING CLINICAL TRIAL
8.1
PRIMARY OBJECTIVE
The primary objective of this study was to evaluate the safety of PROGEL™ PALS including the PROGEL™ Extended Applicator
Spray Tip as an adjunct to standard closure technique in sealing or reducing visible pleural air leaks in patients undergoing
video or robotic-assisted thoracoscopic lung surgery. The secondary objective was to evaluate the efcacy of PROGEL™ PALS for
subjects who remain air leak free following surgery up to one (1) month follow up.
8.2
STUDY DESIGN
The study was a prospective, multi-center, single arm study. Eligible patients were adults undergoing video or robotic-assisted
thoracic lung resection surgery that had intra-operative air leak(s) of any size after standard visceral pleural closure techniques
were applied. Patients were excluded if they had undergone previous lung resection or previous use of a sealant for air leaks,
had a serum creatinine of greater than or equal to 2.5 mg/dl or on dialysis, had a known hypersensitivity to human albumin,
had necrotic or friable borders that will not support secure suture xation if use of sutures is required, if pregnant and/or breast
feeding, or any condition that in the investigator’s opinion would preclude the use of the study device or from completing the
follow-up.
A total of 112 subjects were treated in this study at 15 U.S. sites with a split of 40 video and 72 robotic- assisted procedures to
have at least 100 evaluable subjects. Follow-up assessment was scheduled 30 days post-operative.
The safety assessment was the rate of device- and/or procedure-related adverse events reported through one (1) month of
postoperative follow-up as compared to a performance goal from the published literature. Events were adjudicated by an
independent Clinical Events Committee (CEC). The nal study results are presented below.
*Subjects may be counted more than once in each category if they had multiple procedures in one surgery.
TABLE 19. Volume of PROGEL™ Pleural Air Leak Sealant Used
Volume of PROGEL™ PALS Used per AL (ml)
N
133
Mean
4.6
SD
1.99
Median
4
Minimum
0
Maximum
12
Number of Progel™ PALS Applications
0*
1 (0.7%)
1
108 (80.6%)
2
19 (14.2%)
3
6 (4.5%)
*One air leak became not visible after application of standard procedure, as a result not treated with PROGEL™ PALS.
8.3
ADVERSE EVENTS
Overall, 131 AEs were reported in 59 PROGEL™ subjects during the minimally invasive study (52.7%; 59/112) as compared to the
overall AE rate in the original pivotal study of 65% (76/103) for PROGEL™ and 74.1% (43/58) for the Control cohort. There were
no device related adverse events or unanticipated adverse events in this study. The majority of AEs reported were mild (25%) or
moderate (18.8%) in severity. Forty SAEs occurred in 28 subjects (25%). The majority of SAEs were pulmonary and expected
events as part of a lung resection surgery. Two patients died during the course of the study, one due to cardiac arrest and another
due to multi-system organ failure; neither were device related or unanticipated.
14
16
9
A.
(cont.)
(cont.)
TABLE 20. Incidence of AEs Reported for subjects in Minimally
Invasive Study as Compared to Original Pivotal Study
8.4
Open
Progel PALS
N = 103
Open
Control
N = 58
Minimally Invasive
Progel PALS
N = 112
Number of Subjects with at least one AE
76 (65.0%)
43 (74.1%)
59 (52.7%)
Fever/Pyrexia
22 (21.4%)
12 (20.7%)
12 (10.7%)
Preferred Term
12 (11.7%)
7 (12.1%)
NR
Dyspnea
12 (11.7%)
10 (17.2%)
1 (0.9%)
Constipation
11 (10.7%)
6 (10.3%)
NR
Nausea
10 (9.7%)
7 (12.1%)
NR
Pneumothorax
9 (7.8%)
Confusion
8 (7.8%)
5 (8.6%)
NR
Hypotension
8 (7.8%)
6 (10.3%)
5 (4.5%)
Anemia
8 (7.8%)
6 (10.3%)
NR
Pain
7 (6.8%)
4 (6.9%)
3 (2.7%)
7 (6.8%)
5 (8.6%)
1 (0.9%)
Tachycardia
7 (6.8%)
6 (10.3%)
NR
Death
5 (4.9%)
4 (6.9%)
2 (1.8%)
Oliguria
5 (4.9%)
1 (1.7%)
1 (0.9%)
Vomiting
5 (4.9%)
7 (12.1%)
1 (0.9%)
Pneumonia
5 (4.9%)
7 (12.1%)
3 (2.7%)
4 (3.9%)
0 (0.0%)
NR
Chest Pain
4 (3.9%)
1 (1.7%)
NR
Pleural Effusion
4 (3.9%)
3 (5.2%)
6 (5.4%)
Urinary Retention
3 (2.9%)
0 (0.0%)
2 (1.8%)
Ileus
3 (2.9%)
0 (0.0%)
1(0.9%)
3 (2.9%)
0 (0.0%)
NR
Abdominal Pain
3 (2.9%)
0 (0.0%)
1 (0.9%)
Arrhythmia
3 (2.9%)
0 (0.0%)
NR*
Extrasystoles
3 (2.9%)
0 (0.0%)
NR
Coughing
3 (2.9%)
1 (1.7%)
1 (0.9%)
5 (8.6%)
3 (2.9%)
1 (1.7%)
3 (2.9%)
1 (1.7%)
NR
3 (2.9%)
1 (1.7%)
2 (1.8%)
Hyperkalemia
2 (1.9%)
0 (0.0%)
1(0.9%)
Hyponatraemia
2 (1.9%)
0 (0.0%)
2 (1.8%)
Cardiac Arrest
2 (1.9%)
0 (0.0%)
1 (0.9%)
2 (1.9%)
0 (0.0%)
NR
2 (1.9%)
0 (0.0%)
NR
Asthenia
2 (1.9%)
0 (0.0%)
NR
2 (1.9%)
0 (0.0%)
TABLE 21. Rate of AEs Related to the Study Device and/or Procedure Through the 1-Month Follow-up
(mITT Population) and Identied in the Literature Used to Set the Performance Goal for the Primary Endpoint
Rate of AEs Related to the study device and/or procedure
Rate of AEs Related to the study device
Rate of AE’s Related to the study procedure
8.5
Subjects
N = 112
90% CI
P-value
26/106 (24.5%)
(17.8%, 32.4%)
0.0003
0/106 (0%)
NA
NA
26/106 (24.5%)
(17.8%, 32.4%)
0.0003
KEY SECONDARY EFFICACY ENDPOINT
The key secondary efcacy endpoint of the proportion of subjects without postoperative air leaks (POAL) following surgery
through the 1 month follow-up was 49.1% (p < 0.001), providing strong evidence suggesting the use of PROGEL™ PALS in
minimally invasive procedures is as effective in preventing POALs as in open surgeries.
TABLE 22. Percentage of subjects who remained air leak-free through the 1 MFU
No POAL
Total
(n = 112)
55 (49.1%)
With POAL
57 (50.9%)
Air Leak Status through 1 MFU
P-value*
< 0.001
*As compared to a 23% Performance Goal based on the PMA Pivotal thoracotomy study PROGEL™ PALS group.
4 (3.6%)
ECG Abnormal
An additional analysis was performed on the performance goal studies excluding several of the non-serious AEs reported in
the VATS/Robotics study such as fevers/pyrexia, hypotension, hypoxia, catheter site cellulitis, hypoesthesia, pleural effusion,
procedural pain, productive cough, and abdominal distension. When these events were excluded from the primary endpoint
analysis, the observed incidence of procedure-and/or device-related AEs at one month was 24.5% which met the primary
endpoint performance goal criteria (p = 0.0003).
2 (1.8%)
Hypoxia
PRIMARY SAFETY ENDPOINT
Out of 106 evaluable subjects, the observed incidence of procedure- and/or device-related AEs at one month was 42.5% (90% CI
34.3%, 50.9%), which did not meet criteria for meeting the performance goal of an upper bound less than 42% (p-value = 0.5784).
There were no device-related adverse events and no unanticipated adverse device effects (UADE) reported in this study through
the one-month follow-up. The majority of the procedure-related adverse events were of mild severity and were non-serious,
20.8% (22/106) and 23.6% (25/106), respectively. The most common non-serious procedure-related AEs included fevers/pyrexia
(11.3%; 12/106), hypotension (4.7%; 5/106), hypoxia (3.8%; 4/106), and supraventricular arrhythmia (3.8%; 4/106); all of which
occurred early in-hospital stay prior to discharge, and are known common post-surgical events. When the results were analyzed
for the clinically relevant events of serious or moderate/severe, the observed complication rate was 19.0% (20/105) (serious) or
21.9% (23/105) (moderate/severe) procedure-related adverse events.
8.6
TABLE 23. IOAL Closure Summary
Total
After PROGEL™ PALS IOAL size
2 (1.9%)
1 (1.7%)
NR
Abdomen Enlarged/Distension
2 (1.9%)
1 (1.7%)
1 (0.9%)
Atelectasis
2 (1.9%)
2 (3.4%)
6 (5.4%)
2 (1.9%)
2 (3.4%)
NR
No IOAL
107/133 (80.5%)
< 2 mm
24/133 (18.0%)
2 - 5 mm
2/133 (1.5%)
> 5 mm
0/133 (0.0%)
TABLE 24. Summary of POALs in the Recovery Room
NR
Somnolence
OTHER SECONDARY EFFECTIVENESS ENDPOINTS
Response
No AL
Total
(n = 112)
68 (60.7%)
Occasional Intermittent Bubbles
22 (19.6%)
Frequent Bubbles, Not Continuous
12 (10.7%)
Continuous Bubbles
8 (7.1%)
Missing
0 (0.0%)
17
Preferred Term
Open
Progel PALS
N = 103
Open
Control
N = 58
Minimally Invasive
Progel PALS
N = 112
2 (1.9%)
1 (1.7%)
1 (0.9%)
Anxiety
1 (1.0%)
1 (1.7%)
1(0.9%)
Withdrawal Syndrome
1 (1.0%)
1 (1.7%)
NR
GI Hemorrhage
1 (1.0%)
1 (1.7%)
Hypokalemia
1 (1.0%)
1 (1.7%)
NR
Arrhythmia Atrial
1 (1.0%)
1 (1.7%)
5 (4.5%)*
Respiratory Disorder/distress
1 (1.0%)
1 (1.7%)
2 (1.8%)
1 (1.0%)
1 (1.7%)
NR
Sepsis
1 (1.0%)
1 (1.7%)
NR
1 (1.0%)
1 (1.7%)
1 (0.9%)
1 (1.0%)
1 (1.7%)
NR
Pruritus
1 (1.0%)
2 (3.4%)
NR
Delirium/mental stats changes
1 (1.0%)
2 (3.4%)
3 (2.7%)
Hypertension
1 (1.0%)
2 (3.4%)
NR
Angina Pectoris
1 (1.0%)
2 (3.4%)
NR
Hemoptysis
1 (1.0%)
3 (5.2%)
NR
Arthropathy
0 (0.0%)
1 (1.7%)
NR
Gall Bladder Disorder
0 (0.0%)
1 (1.7%)
NR
Cachexia
0 (0.0%)
1 (1.7%)
NR
19
TABLE 25. Duration of Post-Operative Air Leaks (POAL)
Duration POAL (days)
0 day
1-2 days
3-4 days
5-7 days
> 7 days
Missing
n
Mean
SD
Median
Minimum
Maximum
NR
Total
(n = 112)
55 (49.1%)
32 (28.6%)
7 (6.3%)
6 (5.4%)
11 (9.8%)
1 (0.9%)
111
2.8
6.75
1.0
0.0
46
TABLE 26. Summary of Chest Tube Duration (mITT Population)
Chest Tube Duration (days)*
1-2 days
3-4 days
5-7 days
> 7 days
Missing
N
Mean
Std
Median
Min-Max
Total
(N = 112)
56 (50.0%)
30 (26.8%)
12 (10.7%)
13 (11.6%)
1 (0.9%)
111
4.3
6.02
2.0
1.0 - 46
*If the leak stop date was missing, then the chest tube removal date was regarded as leak stop date.
Dehydration
0 (0.0%)
1 (1.7%)
NR
Non-protein Nitrogen Increased
0 (0.0%)
1 (1.7%)
NR
Edema Dependent
0 (0.0%)
1 (1.7%)
NR
Edema Generalized
0 (0.0%)
1 (1.7%)
NR
Hospital Stay Duration (days)
Fibrillation Ventricular
0 (0.0%)
1 (1.7%)
NR
Cardiac Failure
0 (0.0%)
1 (1.7%)
NR
Hypoventilation
0 (0.0%)
1 (1.7%)
1 (0.9%)
Thrombocytopenia
0 (0.0%)
1 (1.7%)
NR
Allergic Reaction
0 (0.0%)
1 (1.7%)
NR
Fatigue
0 (0.0%)
1 (1.7%)
NR
Rigors
0 (0.0%)
1 (1.7%)
1-2 days
3-4 days
5-7 days
> 7 days
Missing
N
Mean
Std
Median
Min-Max
TABLE 27. Summary of Hospital Duration (mITT Population)
NR
Total
(N = 112)
30 (26.8%)
40 (35.7%)
24 (21.4%)
16 (14.3%)
2 (1.8%)
110
4.6
3.48
3.0
1.0 - 20
Infection, Fungal
0 (0.0%)
1 (1.7%)
NR
Healing, Impaired
0 (0.0%)
1 (1.7%)
NR
Cramps, Legs
0 (0.0%)
1 (1.7%)
NR
The physician should discuss the following with patients potentially receiving PROGEL™ PALS:
9.0
PATIENT COUNSELING INFORMATION
Acidosis, Respiratory
0 (0.0%)
1 (1.7%)
NR
• The Indication for PROGEL™ PALS use
Chyle, Leak
0 (0.0%)
1 (1.7%)
NR
• The risk/benet issues associated with PROGEL™ PALS use.
**
**
10 (8.9%)
Urinary tract infection
0 (0.0%)
0 (0.0%)
5 (4.5%)
Dysuria
0 (0.0%)
0 (0.0%)
2 (1.8%)
Pulmonary Air Leakage
Pneumonia Aspiration
0 (0.0%)
0 (0.0%)
2 (1.8%)
Pulmonary haemorrhage
0 (0.0%)
0 (0.0%)
2 (1.8%)
•
The presence of HSA prepared from pooled human plasma donors in the nal product. Use of this product presents some
risk of transmitting infectious agents. While this risk is deemed remote, it cannot be totally excluded. This also applies to
pathogens that are as yet unknown.
The Human Serum Albumin (HSA-USP) used to manufacture the PROGEL™ PALS is obtained from a U.S. Food and Drug
Administration (FDA) licensed supplier and is derived from plasma collected from donors who have been previously screened
and tested according to the methods specied by the FDA. These methods are designed to minimize the possibility that blood
drawn from donors will contain communicable diseases or viruses such as hepatitis and HIV.
NR= Not Reported
*Term used in VATS/Robotics study was the more specic term of “arrhythmia supraventricular”. See Arrhythmia Atrial.
**Pulmonary air leakage was not reported as an adverse event and included as part of the efcacy data for the Open PMA study.
18
10
20
10.0 INSTRUCTIONS FOR USE
Step 7
Step 11
PROGEL™ Pleural Air Leak Sealant is a single use device intended for application to visceral pleura after standard visceral pleural
closure with, for example, sutures or staples, of visible air leaks incurred during resection of lung parenchyma.
Wipe the applicator tip with clean, sterile gauze to remove any
liquid that may have been expressed with the air. Avoid mixing of
components: do not wipe from one cartridge opening across to
the other – wipe each opening separately.
Rinse the visceral pleural surface to be treated with sterile saline
to remove any pooled blood or blood clots with irrigation and/
or suction.
ASSESS AIR LEAKS AFTER STANDARD SUTURE/STAPLE CLOSURE
After applying standard suture/staple closure methods to seal air leaks, assess for persistent air leaks from the visceral
pleura. If visible air leaks from the visceral pleura are observed, consider applying the PROGEL™ PALS.
If a patient is a candidate for PROGEL™ PALS use, perform the following steps:
INSPECT PACKAGING
The PROGEL™ PALS kit consists of two sealed, sterile packages. Contents:
• One (1) – Chemistry Kit, e-beam sterilized
• One (1) – Applicator Kit, ethylene oxide sterilized
Step 12
• One (1) – Instructions For Use insert (Labeling)
Inspect the packages before opening. Do not use PROGEL™ PALS after the expiration date, because sterility or
performance may be compromised. If package and/or product integrity have been compromised (i.e. damaged
package seal, or broken glass), do not use or resterilize the contents. Refer to other precautions as listed in the
beginning of this labeling.
PREPARE PROGEL™ PLEURAL AIR LEAK SEALANT
Using aseptic technique, open the sterile package and pass the following contents into the sterile eld. Cartridges
may be assembled into the delivery system in any order. Load each cartridge as follows:
• One (1) - pre-loaded cartridge containing 2 ml of processed Human Serum Albumin
Wipe Nose Clean
IMPORTANT: Blot the target tissue area with a sponge or gauze
to remove excess moisture.
Step 8
Place a spray tip on the tip of the applicator and rotate the spray
tip clockwise 1/4 turn until locked. Alternatively, a PROGEL™
Extended Applicator Spray Tip may be used (sold separately).
For complete instructions on use of the PROGEL™ Extended
Applicator Spray Tip, please reference complete labeling
included with the product. REF PGEN005-06, PGEN005-11.
NOTE: This cartridge can be identied by examining the differences between the two contents. The Human
Serum Albumin cartridge is in liquid form and has a slight yellow tint to the solution.
• One (1) - pre-loaded cartridge containing 260 mg of Polyethylene glycol di-succinimidyl succinate (PEG-(SS)2) as
a dried white powder.
Step 13
Ventilation to the affected area should be stopped. If
ventilation needs to be maintained, reducing the tidal volume
is recommended to minimize air leakage and lung movement
during application of the sealant. In procedures where CO2
insufation is being used, consider reducing or discontinuing
CO2 pressure during PROGEL™ PALS application and for the
duration of the sealant set time.
NOTE: This cartridge can be identied by examining the differences between the two contents. The cross-linker
cartridge containing the Polyethylene glycol di-succinimidyl succinate (PEG-(SS)2) is in the form of a white
powder.
• One (1) - 3 ml plastic syringe with 0.5 inch 26 gauge needle
• One (1) - 5 ml vial of USP sterile water for injection (used for reconstitution of the PEG-(SS)2)
Attach Spray Tip
• One (1) - Applicator assembly with locking push rod
Step 9
Step 14
The PROGEL™ PALS is ready for application.
Select the target site to be sealed. NOTE: Each 4 ml applicator
will supply enough PROGEL™ PALS to cover an area 40 cm2
(6 in2) and 1 mm thick.
Apply PROGEL™ PALS
Step 10
After applying standard suture/staple closure methods to seal
identied air leaks, assess for persistent visible air leaks from the
visceral pleura. If visible air leaks from the visceral pleura, note
location of leak and consider applying PROGEL™ PALS. Do not
use more than 30 ml of PROGEL™ PALS per patient.
21
23
Step 1
Step 4
Step 15
Step 16
Using the 3 ml syringe, draw 2 ml of sterile water into the syringe
and express all air in the syringe (syringe and sterile water are
provided in the Applicator Kit).
Without the spray tip attached, point the applicator injection tip
up and load each cartridge into the twin-chambered applicator
housing. Gently press the cartridges to seat them into place.
Hold the spray tip approximately 5 cm (2 in) from the tissue to
be sealed, and apply rm, steady pressure to the push rod to
dispense the gel to the target location. NOTE: The gel can be
applied in either a spray pattern or a stream depending upon
the amount of pressure applied to the push rod. Applying a light
pressure will cause the gel to be dispensed in a stream. Applying
slightly more pressure to the push rod will cause the stream to
convert to a spray.
Maintain rm pressure on the
push rod and move the spray tip
from side to side along the margin
of the tissue surface to be sealed.
NOTE: When properly loaded the chemistry cartridges should
sit ush with the end of the applicator housing.
Interruption of the application for approximately 10 seconds may
result in occlusion of the spray tip. If occlusion occurs, remove
the spray tip, wipe the end of the applicator to remove any
uid, and attach a new spray tip (provided) onto the end of the
applicator as described in step 8.
Draw 2 ml Sterile Water
Keep the applicator tip approximately 5 cm (2 in) away from the
target area to avoid creating bubbles in the sealant material and
apply with a smooth sweeping motion. The formation of bubbles
may compromise the adherence and/or mechanical properties
of the PROGEL™ PALS.
Step 2
Load HSA and Crosslinker
Cartridges into Applicator
Inject the 2 ml of sterile water into the cartridge containing the
cross-linker, (white powder cartridge provided in the Chemistry
Kit).
NOTE: The Human Serum Albumin cartridge contains a yellow
liquid. Water is only to be injected in to the cross-linker (white
powder) cartridge.
Without the spray tip attached, point the applicator injection tip
straight up to allow any air in the chemistry to rise to the top of
the cartridges. Insert the locking push rod into the openings in
the rear of the cartridges until it snaps into place.
Step 19
Spray
Stream
cartridges.
Inject 2 ml sterile water into the white
powder Crosslinker Cartridge
If the applicator’s contents are not entirely used in the rst
application, immediately remove the spray tip and wipe residual
PROGEL™ PALS components from the applicator tip with clean
dry gauze to prevent the remaining material from activating.
Repeat application requires spray tip replacement with an
unused, sterile tip. An additional spray tip is provided in the kit.
PROGEL™ Extended Applicator Spray Tips are sold separately.
Step 20
If more than one kit is needed, additional kits should be prepared
and applied as needed.
Step 3
Mix water and the cross-linker in the cartridge by gently rocking the
cartridge from end to end (generally 1-2 minutes) until the solution
contains no undissolved powder. When all powder is dissolved,
the cross-linker is ready for use.
11.0 HOW SUPPLIED
Insert the Locking Push Rod
NOTE: The PROGEL™ PALS should be used within 20 minutes after
dissolving the cross-linker in water.
20
min
4
Step 18
PROGEL™ PALS application over an air leak site that leaks
despite standard methods of closure may be repeated up to a
total of 3 applications per site if necessary to seal the air leak.
Thereafter, other methods for sealing an air leak should again
be considered.
Step 5
NOTE: During applicator assembly, the PROGEL™ push rod is
designed to lock in to the applicator housing. Forced removal
of the locking push rod from the applicator housing may result
in potential damage to the applicator system or the chemistry
12
Step 17
Allow the PROGEL™ PALS to cure for 15-30 seconds, forming
a exible hydrogel. Two minutes after application, the sealant’s
success in sealing the target site(s) can be tested using the
saline submersion test or by irrigating the site to check for air
bubbles.
STERILE: PROGEL™ Pleural Air Leak Sealant is supplied sterile, with total reconstituted component volume of 4 ml per PROGEL™ PALS
unit. It is intended for single use only. Non-pyrogenic. Do not use if package is opened or damaged.
Step 6
12.0 STORAGE
With the tip of the applicator pointed upward, briskly ick the
applicator to free any air bubbles. Express the air by gently but
rmly pushing up on the push rod until the stoppers in each
cartridge are aligned with one another. Take care to express as
little uid as possible during this process.
NOTE: Store PROGEL™ PALS within the recommended temperature range. Failure to do so may result in poor product performance.
PROGEL™ PALS should be refrigerated between 2°C and 8°C (36°F to 46°F). Do not freeze.
Bard, Davol and Progel are trademarks and/or registered
trademarks of C. R. Bard, Inc. or an afliate.
© Copyright 2015, C. R. Bard, Inc.
All rights reserved.
Mix
Express Air
22
M-00368 2015/02/11
DAV/PALS/0215/0042
Manufactured by:
Neomend, Inc.
60 Technology Drive
Irvine, CA 92618
Customer Service: 1-888-776-4351
24
11
B.
(cont.)
Kit Setup Instructions
1. Preparation – Sterile Field
Step 1
Step 2
Draw 2 ml of
sterile water
Step 3
Inject 2 ml sterile
water into the white
powder crosslinker
cartridge
Step 4
Load cartridges
Mix for 1-2 minutes
until powder
is dissolved
NOTE: Properly
loaded cartridges
will sit flush with
the end of the
applicator housing
NOTE: Progel™
Pleural Air Leak
Sealant must be
used within 20
minutes of mixing
Step 5
Step 6
Express air
Insert locking
push rod
NOTE: Once
inserted, the push
rod should not be
removed
Step 7
Step 8
Wipe nose clean
Attach spray tip
NOTE: Avoid mixing
of components; do
not wipe from one
cartridge opening
across the other
NOTE: An Extended
Applicator Spray Tip
may alternatively
be used (sold
separately)
See full product labeling for complete instructions for use.
12
C.
Application Instructions
2. Application
Step 1
Step 2
Assess for visible
air leaks
Step 3
Rinse with sterile
saline to remove
any pooled blood
or blood clots
Step 4
Stop ventilation to
affected area or
reduce tidal volume
Blot the target
tissue area with a
sponge or gauze
Step 5
If applicable,
consider reducing or
discontinuing
CO2 insufflation
during Progel™ PALS
application
Step 6
Hold spray tip
approximately 2”
from tissue to
be sealed
Varying pressure
applied to push
rod allows for
application as a
stream or spray
Step 7
Step 8
Maintain firm
pressure and
move the spray
tip from side to
side aimed at
the leak
A flexible hydrogel
is formed within
15-30 seconds
For best results,
wait 2 minutes after
application before
irrigating or
performing
a submersion test
See full product labeling for complete instructions for use.
13
3. Clinical Data
A.
Relevant Studies & Publications
The following are relevant studies and publications to help you evaluate the clinical efficacy of
Progel™ Pleural Air Leak Sealant and the value of a proactive strategy for identifying and treating
air leaks during lung surgery.
DISCLAIMER:
The data presented herein is not intended to imply clinical product performance and/or circumvent sound clinical judgment.
14
DISCLAIMER:
15
3. Clinical Data
A.
(cont.)
Relevant Studies & Publications (cont.)
DISCLAIMER:
16
DISCLAIMER:
17
3. Clinical Data
B.
(cont.)
Economic Value Proposition
How does Progel™ Pleural Air Leak Sealant provide economic value?
As many as 58% of lung surgery patients will have an air leak in the OR.1 More than 15% will develop a prolonged
air leak after surgery lasting 7 or more days.2 Management of these postoperative air leaks requires monitoring and
treatment via chest tube, is associated with pain, adds ancillary treatment costs and prolongs hospitalization.
Without prompt and effective treatment, air leaks can potentially lead to serious complications such as pneumonia,
atelectasis or pleural effusion. Identifying and treating air leaks intraoperatively provides the best chance for preventing
prolonged air leak, minimizing associated complications and comorbidities, and providing incidental cost-of-care savings.3
Progel™ is the only sealant approved by the FDA to seal pleural air leaks during lung surgery.1
Sample Analysis C. R. Bard General Hospital*
A
Average number of lung resections performed annually
B
% of patients with inpatient stay extended by air leak complications
C
Additional length of stay per patient with an air leak complication (days)
1.91
D
Total additional length of stay for all patients with air leak complications (days)
CALCULATION: A x B x C
36
E
Average cost for 1 day hospital stay – ICU
F
% of lung resection patients with postoperative ICU stay
G
Average cost for 1 day hospital stay – Floor
H
% of lung resection patients with postoperative Floor stay
I
Estimated cost of complications for patients with a prolonged air leak
CALCULATION: (D x E x F) + (D x G x H)
J
for a list of potentially applicable procedures, please reference the Reimbursement section of this kit
Estimated usage of Progel™ Pleural Air Leak Sealant
based on treatment of all intraoperative air leaks identified in the OR
K
Annual procedural cost associated with use as indicated of Progel™
CALCULATION: A x J x $8504
L
Potential cost-of-care savings associated with use as indicated of Progel™
CALCULATION: (I – K)
120*
15.6%2
$3,000*
25%*
$2,000*
75%*
$81,000
58%1
$59,160
$21,840
* This information is provided as an example only and may not adequately reflect procedural volumes or costs at every hospital where lung surgery is performed in the US.
2 Brunelli et al. Predictors of prolonged air leak after pulmonary lobectomy. Ann Thorac Surg 2004; 77: 1205-1210. Based on the reported incidence of prolonged postoperative air leak.
3 Lackey, Adam M. et al. The cost of air leak: Physicians’ and patients’ perspectives. Thorac Surg Clin 2010, 407-11.
4 Based on a list price of $850 for each 4 mL kit of Progel™ Pleural Air Leak Sealant.
18
19
4. Reimbursement
HCPCS Supply Code
Progel™ Pleural Air Leak Sealant is only indicated for inpatient procedures, and therefore is not associated with any C-code.
CPT Procedure Codes
Lung and Pleura (Open Approach)
32480
Removal of lung, other than pneumonectomy; single lobe (lobectomy)
32482
Removal of lung, other than pneumonectomy; 2 lobes (lobectomy)
32484
Removal of lung, other than pneumonectomy; single segment (segmentectomy)
32491
Removal of lung, other than pneumonectomy; with resection-plication of emphysematous lung(s) (bullous or non-bullous) for lung
volume reduction, sternal split or transthoracic approach, includes any pleural procedure, when performed
32505
Removal of lung, other than pneumonectomy; single segment (segmentectomy)
ICD-9 Procedure Codes
Lung Procedures (Open Approach)
32
Excision of lung and bronchus and Resection of Lung
32.22
Lung volume reduction surgery
32.3
Segmental resection of lung
32.4
Lobectomy of lung
DRG Classification
DRG Classification Dependent on Combination of ICD-9 Procedure and ICD-9 Diagnostic Codes
(determines hospital payment)
163
Major chest procedure with MCC
164
Major chest procedure with CC
165
Major chest procedure without CC/MCC
The codes referenced above are intended for informational/educational purposes only. They should be used only when consistent with the surgeon’s operative dictation and the
Progel™ Instructions For Use.
CPT Copyright 2014 American Medical Association. All rights reserved.
The DRGs shown are the predominant ones for these procedures but not an exhaustive list.
C. R. Bard, Inc. does not guarantee that the procedures described herein will be reimbursable, in whole, or in part, by any public or private payor, representation or warranty relating to reimbursement.
20
5. Competitive Information
A.
Sealant & Hemostat Indication Overview
Product
Manufacturer
Indication
Progel™
Pleural Air Leak
Sealant
Bard Davol Inc.
Progel™ Pleural Air Leak Sealant is a single use device intended for application to visceral
pleura after standard visceral pleural closure with, for example, sutures or staples, of
visible air leaks incurred during resection of lung parenchyma.1
COSEAL®
Surgical Sealant
Baxter
COSEAL® is indicated for use in vascular reconstructions to achieve adjunctive hemostasis
by mechanically sealing areas of leakage.
TISSEEL™
Fibrin Sealant
Baxter
Hemostasis: TISSEEL™ is a fibrin sealant indicated for use as an adjunct to hemostasis
in patients undergoing surgery when control of bleeding by conventional surgical
techniques (such as suture, ligature, and cautery) is ineffective or impractical.
TISSEEL™ is effective in heparanized patients.
Sealing: TISSEEL™ is a fibrin sealant indicated as an adjunct to standard surgical
techniques (such as suture and ligature) to prevent leakage from colonic anastomoses
following the reversal of temporary colostomies.3
EVICEL®
Fibrin Sealant
ETHICON™
EVICEL® is a fibrin sealant indicated as an adjunct to hemostasis for use in patients
undergoing surgery, when control of bleeding by standard surgical techniques
(such as suture, ligature or cautery) is ineffective or impractical.4
Ethicon™ OMNEX™
Surgical Sealant
ETHICON™
ETHICON™ OMNEX™ is indicated for use as an adjunct to standard methods
of achieving hemostasis in vascular reconstruction procedures by mechanically sealing
areas of leakage .5
BioGlue®
Surgical Adhesive
DuraSeal™
Dural Sealant System
CryoLife, Inc.
Integra LifeSciences
BioGlue® is indicated for use as an adjunct to standard methods of achieving
hemostasis (such as sutures and staples) in adult patients in open surgical
repair of large vessels (such as aorta, femoral, and carotid arteries).6
The DuraSeal™ Dural Sealant System is intended for use as an adjunct to
sutured dural repair during cranial surgery to provide watertight closure .7
Progel™ Pleural Air Leak Sealant is the only sealant approved by the FDA and
indicated to seal pleural air leaks in both open and minimally invasive thoracic surgery.1
1. PROGEL™ Pleural Air Leak Sealant Instructions For Use. M-00368.
2. COSEAL® Surgical Sealant Instructions For Use. 0700169 Rev. 4 Date 03/2009. Reviewed 12/4/2014
3. TISSEEL™ Fibrin Sealant Instructions For Use. Revised 09/2013. Reviewed 12/4/2014
4. EVICEL® Fibrin Sealant Instructions For Use. Revised: 01/2014. Reviewed 12/4/2014
5. Ethicon™ Omnex™ Surgical Sealant Instructions For Use. PM72403A 06/2010. Reviewed 12/4/2014
6. BioGlue® Surgical Adhesive Instructions For Use. L6312.007 (06/2010). Reviewed 12/4/2014
7.DuraSeal™ Dural Sealant System Instructions For Use. LCN80 2005 151 Rev. B. Reviewed 12/4/2014
DISCLAIMER: The information presented here is not intended to circumvent sound clinical judgment.
21
5. Competitive Information
B.
(cont.)
Sealant Characteristic Comparison1
OPTIMAL ADHERENCE
The lungs are a dynamic organ, with a structure and function that is uniquely their own. In order to be
effective, a pleural air leak sealant must possess the ideal mechanical properties to create and maintain an
air tight seal with the lung.
Gel Time
While it’s important that a sealant transitions
from a liquid to a hydrogel relatively quickly,
a gel time that is too short may not allow for
complete or adequate adherence.
1
(seconds)
20
15
10
5
0
DuraSeal™
COSEAL®
Progel™ PALS TISSEEL™
BioGlue®
An ideal air leak sealant should have sufficient
elasticity to expand and contract with the lung
throughout the respiratory cycle.
Elasticity1
ELASTICITY
(Elongation, Young's Modulus, kPa)
0.000
0.020
0.040
0.060
0.080
*
1.000
DuraSeal™
COSEAL®
**
BioGlue®
* TISSEEL™ could not be handled without disruption and test was considered failed.
** BioGlue® was significantly less elastic than the other products, with a Modulus
of 11.91.
STRENGTH
Strength1
(burst strength at t = 0 post-application, mmHg/mm)
200
150
100
50
0
DuraSeal™
COSEAL®
Sealants designed for bleeding or fluid leaks set-up
very quickly, in as little as 1-2 seconds.1 Progel™
PALS is designed to gel in 15-30 seconds, and is
specially formulated to flow into staple lines and
defects to create and maintain optimal adherence.
BioGlue®
The proprietary Polyethylene Glycol (PEG)
component of Progel™ PALS is a linear molecule
which lends the hydrogel its ability to stretch. Each
active PEG cross-links with two large, globular Human
Serum Albumin (HSA) proteins to form a three
dimensional structure. The resulting hydrogel is highly
elastic, and can stretch up to 77%.1
In order to effectively seal pleural air leaks,
a lung sealant must be strong enough to
withstand expansion of the lung.
Progel™ PALS creates an air tight seal with the lung
to reinforce primary air leak closure. At full strength
Progel™ PALS can tolerate burst pressures up to
160 mmHg, and is designed to resist failure when
the patient coughs or pressure inside the lungs
increases suddenly.
Progel™ Pleural Air Leak Sealant’s unique combination of strength, elasticity and
adherence make it the only sealant FDA approved and clinically proven to seal air leaks.2,3
Theodore, Pierre, et al. Surgical sealant physical characteristics in vitro comparison to mitigate lung air leaks 2012. Davol Inc. In vitro testing. Data on file. In vitro test results may not correlate to clinical
performance. Five samples of each device were included in each in vitro test. The elongation modulus of Progel™ was significantly less than that of BioGlue® (p<0.05) and comparable to that of COSEAL®
and DuraSeal.™ Progel™ burst strength at time zero was significantly greater than that of COSEAL,® TISSEEL,™ BioGlue® and DuraSeal™ (p<0.05).
2
Progel™ Pleural Air Leak Sealant Instructions for Use. M-00368.
3
Allen, Mark S. et al. Prospective randomized study evaluating a biodegradable polymeric sealant for sealing intraoperative air leaks that occur during pulmonary resection.
1
22
C.
Cross Reference Chart
Product
Progel™ Pleural
Air Leak Sealant
COSEAL®
Surgical Sealant
Part Number
PGPS002
EVICEL®
Fibrin Sealant
ETHICON™ Omnex™
Surgical Sealant
BioGlue®
Surgical Adhesive
DuraSeal™
Dural Sealant System
Progel™ Pleural Air Leak Sealant 4 mL (4 per case)
934070
COSEAL® Surgical Sealant, 2 mL
934071
934072
1501261
TISSEEL™
Fibrin Sealant
Description
TISSEEL™ Fibrin Sealant, Pre-Filled 2 mL
1501262
1501263
3901
EVICEL® 1-mL Kit (2 mL)
3902
3905
4901
ETHICON™ OMNEX™ Surgical Sealant (4 units per case)
BG3502-5-US
BioGlue® Syringe 2mL 5 Pack Kit
BG3505-5-US
BG3510-5-US
20-2050
DuraSeal™ Dural Sealant System, 5mL (5 kits/box)
23
6. Information for Materials Managers
A.
Packaging Overview
Progel™ Pleural Air Leak Sealant
Progel™ Pleural Air Leak Sealant 4 mL Kit
Contains: 1 Applicator Kit
16 cm (6") Extended Applicator Spray Tip
29 cm (11") Extended Applicator Spray Tip
Contains: 4 Extended Tips
Contains: 4 Extended Tips
Applicator Spray Tips
Contains: 10 packs of 2 tips
24
1 Chemistry Kit
B.
Storage Requirements
How Supplied1
Progel™ Pleural Air Leak Sealant is supplied as a sterile, single-use, two-component kit. When mixed, each
Progel™ kit makes a 4 mL total sealant volume. Each Progel™ kit includes:
One Chemistry Kit
One Applicator Kit
One Instructions For Use Pamphlet
Storage1
Progel™ Pleural Air Leak Sealant should be stored in a refrigerator between 2°C and 8°C (36°F to 46°F) for a
maximum shelf-life of 2 years. Each unit of Progel™ Pleural Air Leak Sealant is labeled with a lot number and an
expiration date which reflects this 2 year shelf-life. Any Progel™ Pleural Air Leak Sealant kit not used on or before
the expiration date indicated on the product packaging should be discarded.
Please direct any questions regarding appropriate storage of Progel™ Pleural Air Leak Sealant to:
Bard Medical Services & Support: 1.800.562.0027
C.
Product Order Codes
Catalog Number
Quantity
Description
PGPS002
4/cs.
Progel™ Pleural Air Leak Sealant (4mL)
PGST009
10/cs.
Progel™ Applicator Spray Tips (Pack of 2)
PGEN005-11
4/cs.
Progel™ Extended Spray Tip 29 cm (11")
PGEN005-06
4/cs.
1 Progel™ Pleural Air Leak Sealant Instructions For Use. M-00368.
25
6. Information for Materials Managers
D.
(cont.)
Product Evaluation
Evaluate Progel™ Pleural Air Leak Sealant at
your hospital.
Data has shown that intraoperative air leaks will be visible in over 58% of lung resection surgeries if a
submersion test is performed to screen for air leaks during the procedure.1 Progel™ is the only sealant
clinically proven to reduce postoperative air leak complications and length of inpatient hospitalization
when applied to visible leaks during lung surgery.
Take the Progel™ Challenge
See firsthand how Progel™ Pleural Air Leak Sealant can impact surgical and patient outcomes
at your hospital.
1.See the leak
As part of the Progel™ Challenge, surgeons will be asked to perform an intraoperative submersion test to identify
any existing air leaks while the patient is still in surgery.
2.Spray the leak
Once an intraoperative air leak has been identified, surgeons may choose to apply Progel™ Pleural Air Leak Sealant
to reinforce primary air leak closure and create an airtight seal.
3.Seal the leak1
When used as indicated, Progel™ Pleural Air Leak Sealant is clinically proven to:
• Effectively treat intraoperative air leaks.1
• Significantly reduce postoperative air leak complications including prolonged air leaks.1
• Reduce inpatient length of hospitalization by as much as 1.9 days.1
1 Allen, Mark S. et al. Prospective Randomized Study Evaluating a Biodegradable Polymeric Sealant for Sealing Intraoperative Air Leaks That Occur
During Pulmonary Resection. Annals of Thoracic Surgery 2004; 77:1792-1801. Pivotal trial. Davol Inc. Data on file.
Talk to a Bard BioSurgery Representative
about participating in the Progel™ Challenge.
26
7. Surgical Education
Bard BioSurgery is committed to providing you with education
programs designed to help you meet your desired outcome.
Your needs. Your schedule. Your peers.
Bard Surgical education programs are designed to provide you with focused
and flexible modalities providing in-depth education on products and
techniques intended to help you optimize patient care.
Surgeons who participate in the Bard BioSurgery
Surgical Education Program will benefit from:
• Instruction from leading surgeon experts in surgical techniques
• Opportunities to discuss and review surgical experience with peers
• Interactive exchanges with expert surgeons on specific topics
• Opportunities to practice these techniques through hands-on
bioskills labs
We are committed to advanced professional education
– helping you choose the right products and procedures
to provide the right outcomes for your patients.
27
8. Bard’s Value Added Programs
Committed to a Successful Partnership
Healthcare economics and new policies have changed the way you do business. It’s imperative
to work with a partner who understands your challenges, and who delivers both value and
devices that support best-in-class patient care. Bard partners benefit from highly personalized
and valuable services when they take advantage of the full line of BioSurgery products.
Access
As a Bard partner, one of your key benefits is receiving dedicated customer
service and personalized support. Whether it’s placing orders, answering billing
questions, finding cross-references or providing requested documentation, your
dedicated customer service specialist is on call for you.
Bard Customer Service: 1.800.556.6275
Medical Services & Support
Medical Services & Support was created to assist you and your needs
as a medical provider in today’s changing healthcare environment. This
unique support team from Bard will provide you with technical and clinical
information on procedures involving Bard products and/or inquiries.
Our support staff consists of knowledgeable health professionals, including
surgeons, prepared to answer your questions and ready to meet your
resource needs.
Bard Medical Services & Support: 1.800.562.0027
Contact your local Bard BioSurgery representative for more information.
28
Bard’s BioSurgery franchise is delivering a growing line of surgical sealants and hemostats to
complement surgical techniques across thoracic, cardiovascular and other surgical specialties.
Our researchers are constantly engaged in developing new products aimed at providing
exceptional reliability and value – qualities that clinicians, physicians and patients have come
to depend on.
Catalog Number
Quantity
Description
PGPS002
4/cs.
Progel™ Pleural Air Leak Sealant (4mL)
PGST009
10/cs.
Progel™ Applicator Spray Tips (Pack of 2)
PGEN005-11
4/cs.
PGEN005-06
4/cs.
For more information,
visit www.davol.com
Order Form
Please add these marked products to my preference card.
I would like to have these marked products in stock.
I would like to trial these marked products.
Purchase Order Number Date
See full product labeling for complete Instructions For Use and important
safety information.
Catalog Number(s) Quantity
Bard, Davol, Arista, Avitene, and Progel are trademarks or registered
trademarks of C. R. Bard, Inc.
Surgeon’s Signature
© Copyright 2015, C. R. Bard, Inc. All rights Reserved.
Davol Inc. • Subsidiary of C. R. Bard, Inc.
100 Crossings Boulevard • Warwick, RI 02886
1.800.556.6275 • www.davol.com
Medical Services & Support 1.800.562.0027
DAV/PALS/1214/0014(2)

Progel - Davol

Transcription

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