Lung Disease, Pulmonary Lobectomy
Conditions
Keywords
Elective pulmonary resection via open thoracotomy.
Brief summary
To further characterize the PleuraSeal Sealant System as compared to standard of care (sutures and staples only) in subjects undergoing an elective pulmonary lobectomy and segmentectomy via open thoractomy.
Interventions
PROCEDUREStandard Tissue Closure Techniques
Standard Tissue Closure Techniques (sutures and staples only)
DEVICEPleuraSeal Lung Sealant System
Sponsors
Medtronic - MITG
Integra LifeSciences Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Pre-Operative Inclusion Criteria: * Subjects 18 years of age or older * Scheduled for an elective pulmonary lobectomy and segmentectomy (limited resection in case of reduced functional operability) in one or more lobes via an open thoracotomy * Subject or authorized representative has been informed of the nature of the study and has provided written informed consent, approved by the appropriate Ethics Committee of teh respective clinical site Pre-Operative
Exclusion criteria
* Documented history of bleeding disorders and/or severely altered renal or hepatic function * Compromised immune system (e.g., HIV/acquired immunodeficiency syndrome, immunosuppressive therapy) * Prior ipsilateral thoracotomy * Subject with Tuberculosis * Extensive adhesions from previous thoracic trauma or surgery * Undergoing lung volume reduction surgery, wedge resection, pneumonectomy, sleeve resection or bronchoplasty, blebectomy, bullectomy, pleurodesis, lung transplant, or living lobe transplant donor * Subject has active systemic or pulmonary infection * Treated with chronic steroid therapy unless discontinued more than 6 weeks prior to surgery (standard acute perioperative steroids are permitted). For purposes of this protocol, chronic steroid therapy is defined as greater than 4 weeks * Pregnant (documented by pregnancy test), breast-feeding, or that wish to become pregnant during the course of the study or not willing to use birth control (e.g. IUD; oral, transdermal or parenteral contraceptives; abstinence) * Documented history of uncontrolled diabetes * Subject has an estimated life expectancy of less than 6 months * Currently enrolled in another investigational drug or device trial that has not completed the primary endpoint or that clinically interferes with this study * Congestive heart failure, cor pulmonale, or other condition that, in the opinion of the investigator, may jeopardize the subject's well-being and/or negatively impact the interpretation of data collected during the clinical study * Unable to comply with the study requirements or follow-up schedule Intra-Operative Inclusion Criteria: * At least one intra-operative air leak identified during lung submersion leak test after the initial closure is completed * Hemostasis must be confirmed prior to randomization Intra-Operative
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Remaining Air Leak Free From Time of Skin Closure to Hospital Discharge. | 30 days | — |
| Percentage of Subjects Remaining Air Leak Free From Skin Closure to Discharge | 30 days | Sub-analysis by pre-randomization grade of air leak. Grade 1= countable air bubbles, Grade 2= stream of bubbles, Grade 3= coalesced bubbles |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects for Whom Intra-operative Air Leak Sealing Success is Achieved. | Intra-operatively, time of study procedure | Success is defined as no presence of air leak intra-operatively. |
| Time From Skin Closure to Last Observable Air Leak. | 30 days | — |
| Duration of Chest Drainage | 30 days | — |
| Duration of Hospitalization | 30 days | — |
Countries
Austria, Belgium, Netherlands, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Between January 28, 2008 and October 21, 2008, a total of 161 subjects were consented and screened for potential study participation at 8 institutions (hospitals). Of these subjects, 121 were randomized.
Pre-assignment details
Subjects were evaluated for pre-operative and intra-operative eligibility criteria. Randomization occurred intra-operatively.
Participants by arm
| Arm | Count |
|---|---|
| PleuraSeal PleuraSeal Lung Sealant System | 62 |
| Standard of Care Standard tissue closure techniques (control) - sutures or staples only | 59 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Standard of Care | Total | PleuraSeal |
|---|---|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 10.8 | 62.1 years STANDARD_DEVIATION 9.9 | 61.5 years STANDARD_DEVIATION 9.1 |
| Body Mass Index | 26.35 kg/m^2 STANDARD_DEVIATION 4.55 | 26.10 kg/m^2 STANDARD_DEVIATION 4.63 | 25.86 kg/m^2 STANDARD_DEVIATION 4.73 |
| Height | 169.4 cm STANDARD_DEVIATION 9.6 | 169.4 cm STANDARD_DEVIATION 9.1 | 169.5 cm STANDARD_DEVIATION 8.8 |
| Nicotine Use Current | 17 participants | 39 participants | 22 participants |
| Nicotine Use History | 34 participants | 65 participants | 31 participants |
| Nicotine Use Never | 8 participants | 17 participants | 9 participants |
| Race/Ethnicity, Customized African | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Caucasian | 55 participants | 116 participants | 61 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Other | 1 participants | 2 participants | 1 participants |
| Region of Enrollment Austria | 30 participants | 62 participants | 32 participants |
| Region of Enrollment Belgium | 14 participants | 28 participants | 14 participants |
| Region of Enrollment Netherlands | 6 participants | 15 participants | 9 participants |
| Region of Enrollment Switzerland | 5 participants | 6 participants | 1 participants |
| Region of Enrollment United Kingdom | 4 participants | 10 participants | 6 participants |
| Sex: Female, Male Female | 22 Participants | 48 Participants | 26 Participants |
| Sex: Female, Male Male | 37 Participants | 73 Participants | 36 Participants |
| Weight | 75.57 kg STANDARD_DEVIATION 13.96 | 75.00 kg STANDARD_DEVIATION 14.64 | 74.46 kg STANDARD_DEVIATION 15.35 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 62 | 4 / 59 |
| serious Total, serious adverse events | 16 / 62 | 11 / 59 |
Outcome results
Primary
Percentage of Subjects Remaining Air Leak Free From Skin Closure to Discharge
Sub-analysis by pre-randomization grade of air leak. Grade 1= countable air bubbles, Grade 2= stream of bubbles, Grade 3= coalesced bubbles
Time frame: 30 days
Population: Analysis by grade of air leak.Grade 1= countable air bubbles, Grade 2= Stream of bubbles, Grade 3 = Coalesced bubbles.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PleuraSeal | Percentage of Subjects Remaining Air Leak Free From Skin Closure to Discharge | Grade 1 air leak | 37.5 Percentage of participants |
| PleuraSeal | Percentage of Subjects Remaining Air Leak Free From Skin Closure to Discharge | Grade 2/3 air leak | 43.5 Percentage of participants |
| Standard of Care | Percentage of Subjects Remaining Air Leak Free From Skin Closure to Discharge | Grade 1 air leak | 50 Percentage of participants |
| Standard of Care | Percentage of Subjects Remaining Air Leak Free From Skin Closure to Discharge | Grade 2/3 air leak | 15.2 Percentage of participants |
p-value: 0.53Fisher Exact
p-value: 0.013Fisher Exact
Primary
Percentage of Subjects Remaining Air Leak Free From Time of Skin Closure to Hospital Discharge.
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PleuraSeal | Percentage of Subjects Remaining Air Leak Free From Time of Skin Closure to Hospital Discharge. | 41.9 Percentage of participants |
| Standard of Care | Percentage of Subjects Remaining Air Leak Free From Time of Skin Closure to Hospital Discharge. | 30.5 Percentage of participants |
Comparison: Primary objective was to demonstrate superiority of PleuraSeal as an adjunct compared to standard of care alone. Tissue closure rates for the treatment and control groups were assumed to be 0.40 and 0.15, respectively. To achieve 80 percent power (alpha=0.05, 2-tailed, Fisher's Exact Test) required 112 completed subjects. To account for potential subject withdrawals, an additional 8 subjects were to be enrolled for a total of 120 randomized subjects (approx. 60 per treatment group).p-value: 0.257Fisher Exact
Secondary
Duration of Chest Drainage
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| PleuraSeal | Duration of Chest Drainage | 93.68 hours | Standard Deviation 127.88 |
| Standard of Care | Duration of Chest Drainage | 94.05 hours | Standard Deviation 81.05 |
p-value: 0.5592-sample t-test
Secondary
Duration of Hospitalization
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| PleuraSeal | Duration of Hospitalization | 312.0 hours | Standard Deviation 419.2 |
| Standard of Care | Duration of Hospitalization | 288.0 hours | Standard Deviation 254.1 |
p-value: 0.2922-sample t-test
Secondary
Percentage of Subjects for Whom Intra-operative Air Leak Sealing Success is Achieved.
Success is defined as no presence of air leak intra-operatively.
Time frame: Intra-operatively, time of study procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PleuraSeal | Percentage of Subjects for Whom Intra-operative Air Leak Sealing Success is Achieved. | 71 Percentage of participants |
| Standard of Care | Percentage of Subjects for Whom Intra-operative Air Leak Sealing Success is Achieved. | 23.7 Percentage of participants |
p-value: <0.001Fisher Exact
Secondary
Time From Skin Closure to Last Observable Air Leak.
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PleuraSeal | Time From Skin Closure to Last Observable Air Leak. | 6.0 hours |
| Standard of Care | Time From Skin Closure to Last Observable Air Leak. | 30.0 hours |
p-value: 0.79Kaplan-Meier