Emphysema
Conditions
Keywords
COPD, RePneu
Brief summary
Multicenter, randomized, assessor-blinded controlled study of safety and effectiveness of the PneumRx, Inc. RePneu Lung Volume Reduction Coil (RePneu LVRC) System
Detailed description
This will be a prospective, multicenter, randomized, assessor-blinded, controlled study comparing outcomes between the LVRC and Control Groups. Subjects will be block randomized in an LVRC (Treatment) to Control ratio of 1:1. The randomization will be stratified by homogeneous versus heterogeneous emphysema, to support a balance of patients with differing heterogeneity in both the LVRC and Control Groups.
Interventions
The LVRC group will undergo two bronchoscopic sessions under general or moderate sedation. During the procedure, subjects will be treated with Coils according to the Instructions for Use.
Sponsors
PneumRx, Inc.
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
One group received standard of care and LVRC and the control group received only standard of care.
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is greater than or equal to 35 yrs of age * CT Scan indicates bilateral emphysema, as determined by the Core Radiology Lab using the criteria presented in the CT Scoring Plan for Core Radiology Lab * Subject has post-bronchodilator FEV1 less than or equal to 45% predicted * Subject has Total Lung Capacity \>100% predicted * Subject has residual volume (RV) greater than or equal to 175% predicted * Subject has marked dyspnea greater than or equal to 2 on mMRC scale of 0-4 * Subject has stopped smoking for at least 8 weeks prior to entering the study as confirmed by a Cotinine test or other appropriate diagnostic test. * Subject has completed a pulmonary rehabilitation program within 6 mos prior to treatment and/or is regularly performing maintenance respiratory rehabilitation if initial supervised therapy occurred more than 6 mos prior to baseline testing. * Subject has received Pneumococcal and Influenza vaccinations consistent with local recommendations and/or policy. * Subject (and legal guardian, if applicable) has read, understood, and signed the Informed Consent form.
Exclusion criteria
* Subject has severe homogeneous emphysema determined by Core Radiology Lab. * Subject has co-morbidities that may significantly reduce subject's ability to improve exercise capacity (e.g., severe arthritis, planned knee surgery) or baseline limitation on 6MWT is not due to dyspnea. * Subject has a change in FEV1 of greater than 20% (or, for subjects with pre-bronchodilator FEV1 below 1L, a change of greater than 200mL) post-bronchodilator unless investigator can confirm by other means that subject does not have asthma. * Subject has DLCO of less than 20% of predicted. * Subject has severe gas exchange abnormalities, PaCO2 of greater than 55mm Hg; PaO2 of less than 45 mm Hg on room air (high altitude criterion: PaO2 of less than 30mm Hg). * Subject has a history of recurrent clinically significant respiratory infections, defined as 3 hospitalizations for respiratory infection during the year prior to enrollment. * Subject as severe pulmonary hypertension defined by right ventricular systolic pressure of greater than 50mm Hg via right heart catheterization and/or echocardiogram * Subject has an inability to walk \>140m (150 yd) in 6 minutes * Subject has evidence of other severe disease (such as but not limited to lung cancer or renal failure), which in the judgment of the investigator may compromise survival of the subject for the duration of the study. * Subject is pregnant or lactating, or plans to become pregnant within the study timeframe. * Subject has an inability to tolerate bronchoscopy under moderate sedation or general anesthesia. * Subject has clinically significant bronchiectasis. * Subject has giant bullae \>1/3 lung volume * Subject has had previous LVR surgery, lung transplantation, lobectomy or LVR devices or other device to treat COPD in either lung. * Subject has been involved in pulmonary drug or device studies within 30 days prior to this study. * Subject is taking \>20mg prednisone (or equivalent dose of a similar steroid) daily. * Subject requires high level chronic immunomodulatory therapy to treat a moderate to severe chronic inflammatory autoimmune disorder. * Subject is on an antiplatelet agent (such as Plavix) or anticoagulant therapy (such as Heparin or Coumadin) which cannot be stopped for 7 days prior to the procedure. * Subject has any other disease, condition(s) or habit(s) that would interfere with completion of study and follow up assessments, would increase risks of bronchoscopy or assessments, or in the judgment of the investigator would potentially interfere with compliance to this study or would adversely affect study outcomes. * Subject has a sensitivity or allergy to nitinol (nickel-titanium) or its constituent metals. * Subject has a known sensitivity to drugs required to perform bronchoscopy. * Subject has been diagnosed with alpha-1 antitrypsin deficiency (AATD).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Meters: 6 Minute Walk Test - Change From Baseline to 12 Months Follow up | baseline through 12 months follow up | mean absolute change from baseline at 12 months in the 6 Minute Walk Test comparing test and control groups (median if skewed) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| St. George's Respiratory Questionnaire (SGRQ) Mean Absolute Change From Baseline to 12 Months | BL to 12 months | mean absolute difference in SGRQ results comparing BL to 12 months, LVRC vs. Control, score is on a scale from 0 to 100, negative change will be a better outcome. |
| 6MWT Responder Analysis | 12 months | 6MWT Responder Analysis: Responder is defined as those with an improvement of greater than or equal to 25 meters |
| Mean Percent Change in FEV1 From Baseline to 12 Months | BL to 12 months | Mean percent change in FEV1(Forced Expiratory Volume in 1 second) at 12 months (median if skewed) |
Other
| Measure | Time frame | Description |
|---|---|---|
| SGRQ Responder Analysis | 12 months | SGRQ Responder Analysis: Responder defined as those with an improvement greater than or equal to 4 points |
| Residual Volume (RV) Mean Absolute Difference in RV From Baseline to 12 Months | 12 months | Mean absolute difference in RV results measured using plethysmography, comparing BL to 12 months, LVRC vs. Control |
| RV/TLC Mean Absolute Difference From Baseline to 12 Months | 12 months | Mean absolute difference in RV/TLC (residual volume/total lung capacity - a measure done during lung function testing where residual volume is air left over in lung after completely breathing out and total lung capacity is how much air the lung can breathe in) results measured using plethysmography, comparing BL to 12 months, LVRC vs. Control |
Countries
Canada, France, Germany, Netherlands, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RePneu Lung Volume Reduction Coil System The RePneu Lung Volume Reduction Coil System is an implantable device, delivered through a fiber-optic bronchoscope. This is a two part system that consists of 1) sterile Nitinol Coils and 2) a sterile, disposable, single-use (single-patient) Delivery System consisting of a Guidewire, Catheter, Cartridge, and Forceps.
RePneu Lung Volume Reduction Coil System: The LVRC group will undergo two bronchoscopic sessions under general or moderate sedation. During the procedure, subjects will be treated with Coils according to the Instructions for Use. | 158 |
| Control Arm is Standard Medical Care The Control Group will not undergo any bronchoscopies for Coil placement and will not receive prophylactic antibiotics or steroids before and after 'treatment' or chest x-rays in connection with the 'treatment' visits. The frequency of visits to the Study Doctor or designee will be similar to the LVRC Group. | 157 |
| Total | 315 |
Baseline characteristics
| Characteristic | RePneu Lung Volume Reduction Coil System | Control Arm is Standard Medical Care | Total |
|---|---|---|---|
| Age, Continuous | 63.4 years STANDARD_DEVIATION 8.05 | 64.3 years STANDARD_DEVIATION 7.76 | 63.9 years STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 157 Participants | 155 Participants | 312 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 86 Participants | 79 Participants | 165 Participants |
| Sex: Female, Male Male | 72 Participants | 78 Participants | 150 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 10 / 155 | 8 / 157 |
| other Total, other adverse events | 155 / 155 | 142 / 157 |
| serious Total, serious adverse events | 78 / 155 | 44 / 157 |
Outcome results
Primary
Meters: 6 Minute Walk Test - Change From Baseline to 12 Months Follow up
mean absolute change from baseline at 12 months in the 6 Minute Walk Test comparing test and control groups (median if skewed)
Time frame: baseline through 12 months follow up
Population: Patients who were analyzed at 12 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RePneu Lung Volume Reduction Coil System | Meters: 6 Minute Walk Test - Change From Baseline to 12 Months Follow up | 10.3 meters |
| Control Arm is Standard Medical Care | Meters: 6 Minute Walk Test - Change From Baseline to 12 Months Follow up | -7.6 meters |
Secondary
6MWT Responder Analysis
6MWT Responder Analysis: Responder is defined as those with an improvement of greater than or equal to 25 meters
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RePneu Lung Volume Reduction Coil System | 6MWT Responder Analysis | 60 Participants |
| Control Arm is Standard Medical Care | 6MWT Responder Analysis | 41 Participants |
Secondary
Mean Percent Change in FEV1 From Baseline to 12 Months
Mean percent change in FEV1(Forced Expiratory Volume in 1 second) at 12 months (median if skewed)
Time frame: BL to 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RePneu Lung Volume Reduction Coil System | Mean Percent Change in FEV1 From Baseline to 12 Months | 3.8 percentage change |
| Control Arm is Standard Medical Care | Mean Percent Change in FEV1 From Baseline to 12 Months | -2.5 percentage change |
Secondary
St. George's Respiratory Questionnaire (SGRQ) Mean Absolute Change From Baseline to 12 Months
mean absolute difference in SGRQ results comparing BL to 12 months, LVRC vs. Control, score is on a scale from 0 to 100, negative change will be a better outcome.
Time frame: BL to 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RePneu Lung Volume Reduction Coil System | St. George's Respiratory Questionnaire (SGRQ) Mean Absolute Change From Baseline to 12 Months | -8.1 score on a scale | Standard Error 1.08 |
| Control Arm is Standard Medical Care | St. George's Respiratory Questionnaire (SGRQ) Mean Absolute Change From Baseline to 12 Months | 0.8 score on a scale | Standard Error 1.05 |
Other Pre-specified
Residual Volume (RV) Mean Absolute Difference in RV From Baseline to 12 Months
Mean absolute difference in RV results measured using plethysmography, comparing BL to 12 months, LVRC vs. Control
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RePneu Lung Volume Reduction Coil System | Residual Volume (RV) Mean Absolute Difference in RV From Baseline to 12 Months | -0.41 liters | Standard Error 0.081 |
| Control Arm is Standard Medical Care | Residual Volume (RV) Mean Absolute Difference in RV From Baseline to 12 Months | -0.10 liters | Standard Error 0.08 |
Other Pre-specified
RV/TLC Mean Absolute Difference From Baseline to 12 Months
Mean absolute difference in RV/TLC (residual volume/total lung capacity - a measure done during lung function testing where residual volume is air left over in lung after completely breathing out and total lung capacity is how much air the lung can breathe in) results measured using plethysmography, comparing BL to 12 months, LVRC vs. Control
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RePneu Lung Volume Reduction Coil System | RV/TLC Mean Absolute Difference From Baseline to 12 Months | -3.96 percent | Standard Error 0.564 |
| Control Arm is Standard Medical Care | RV/TLC Mean Absolute Difference From Baseline to 12 Months | -0.45 percent | Standard Error 0.554 |
Other Pre-specified
SGRQ Responder Analysis
SGRQ Responder Analysis: Responder defined as those with an improvement greater than or equal to 4 points
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RePneu Lung Volume Reduction Coil System | SGRQ Responder Analysis | 98 Participants |
| Control Arm is Standard Medical Care | SGRQ Responder Analysis | 48 Participants |