Emphysema
Conditions
Keywords
severe heterogeneous emphysema, severe homogeneous emphysema
Brief summary
This study will look at outcomes between Endobronchial Coil Treatment and Control groups in patients with severe heterogeneous and or homogeneous emphysema.
Detailed description
This will be a prospective, multicenter, randomized, controlled study comparing outcomes between the Endobronchial Coil and Control Groups. Subjects will be block randomized in a Treatment to Control ratio of 2:1. The randomization will be stratified by site and homogeneous versus heterogeneous emphysema, to support a balance of patients with differing heterogeneity in both the Treatment and Control Groups
Interventions
DEVICEEndobronchial Coils
Endobronchial Coil implants
Sponsors
PneumRx, Inc.
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Read, understood and signed the Informed Consent form * Meets indications for use per the IFU * Bilateral heterogeneous and/or homogeneous emphysema * Post bronchodilator 15% predicted ≤ Forced Expiratory Volume in 1 second (FEV1) ≤ 45% predicted * Post bronchodilator Residual Volume (RV) ≥ 200% predicted * Post bronchodilator Total Lung Capacity (TLC) \>100% pred. * Post bronchodilator RV/TLC \> 55% * Dyspnea related to hyperinflation scored ≥ 2 on modified Medical Research Council (mMRC) dyspnea scale despite optimal medical management * Receiving optimal drug therapy and medical management according to clinical practice. * Performing regular physical activity, at least 2 times per week * Stopped smoking as confirmed by carboxyhemoglobin (CoHB) * 100m ≤ 6 minute walk distance (6MWD) ≤ 450m * Deemed eligible per Eligibility Review Committee (ERC) * if treated in France, subject must be entitled to French social security.
Exclusion criteria
* Known sensitivity to drugs required for performing bronchoscopy or in whom bronchoscopic procedures are contraindicated * Evidence of active infection in the lungs * Hypersensitivity or allergy to nitinol (nickel-titanium) or its constituent metals * Clinical significant pulmonary fibrosis * Clinically significant, generalized bronchiectasis * Clinically significant bleeding disorders * Patient taking immunosuppressive drugs other than steroids (e.g., for the treatment of cancer, rheumatoid arthritis, autoimmune disease, or prevention of tissue or organ rejection). * Primary diagnosis of asthma * Two (2) or more COPD exacerbations in the prior year, or 1 or more COPD exacerbations in the prior 3 months with indication for hospitalization assessment, according to GOLD 2017 recommendations . * Predominant small airways disease defined as significant bronchiectasis with sputum production (\> 2 tablespoons daily) or significant bronchial wall thickening per High Resolution Computed Tomography (HRCT) * Percent Low Attenuation Area (%LAA) \< 20% in the most damaged lobe of either lung. * Computed Tomography (CT) Imaging consistent with active pulmonary infection, significant interstitial disease or pleural disease * Severe bullous disease (defined by bulla \> 8cm or 1/3 of lung volume, or single bullous defect \>8 cm) or predominant paraseptal emphysema \[defined by numerous large (\>1cm) paraseptal defects in the target lobe comprising of \>5% of total lung volume\]. * Lung pathology of nodule not proven stable or benign * Radiographic confirmation of atelectasis or other scarring/fibrosis in areas of intended Coil implant * Use of more than 20 mg/day prednisolone or equivalent dosage of a different corticosteroid * Severe pulmonary hypertension (Right Ventricular Systolic Pressure (RVSP) \> 50 mm Hg or other signs of Pulmonary Hypertension (PHT) with right ventricular dysfunction) * Severe hypercapnia (PaCO2 \> 55 mmHg on room air) and/or severe hypoxemia (PaO2 \< 45mm Hg on room air, High altitude criterion: PaO2 \< 30 mm Hg) * Previous Lung Volume Reduction (LVR) surgery, lung transplantation, lobectomy, LVR devices or other device to treat COPD in either lung. * Diagnosed with alpha-1 antitrypsin deficiency * Diffusion Capacity of the lungs for Carbon Monoxide (DLCO) \< 20 % * Significant, recent or unstable cardiac disease defined as severe heart failure (Left Ventricular Ejection Fraction (LVEF) \< 45% despite optimal medical management), unstable cardiac arrhythmia or coronary artery disease (angina on activity), or ischemic event in the past 6 months. * Body Mass Index (BMI) \> 30 * Participation in any other clinical Study. * Subject is pregnant or lactating, or plan to become pregnant within the study timeframe. * If treated in France, Subject is a personnel vulnerable as defined by French Regulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in FEV1 at 6 Months | 6 months | Percent change in FEV1 |
| Absolute Change in SGRQ Score at 6 Months | 6 months | Change in SGRQ score - St. George Respiratory Questionnaire from 0 to 100, higher score indicating more limitations (worse), increase in score indicating worse outcome, decrease in score indicating improvement |
Countries
Austria, France, Germany, Italy, Netherlands, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Endobronchial Coils Treatment with PneumRx Endobronchial Coil System
Endobronchial Coils: Endobronchial Coil implants | 80 |
| Control Medically-managed control group | 40 |
| Total | 120 |
Baseline characteristics
| Characteristic | Endobronchial Coils | Control | Total |
|---|---|---|---|
| Age, Continuous | 63.4 years STANDARD_DEVIATION 7.51 | 62.8 years STANDARD_DEVIATION 7.06 | 63.2 years STANDARD_DEVIATION 7.34 |
| Forced Expiratory Volume in 1 second (FEV1) | 0.8 Litres STANDARD_DEVIATION 0.2026 | 0.8 Litres STANDARD_DEVIATION 0.222 | 0.8 Litres STANDARD_DEVIATION 0.21 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 78 Participants | 40 Participants | 118 Participants |
| Sex: Female, Male Female | 41 Participants | 21 Participants | 62 Participants |
| Sex: Female, Male Male | 39 Participants | 19 Participants | 58 Participants |
| St. George Respiratory Questionnaire Score (SGRQ) | 59.327 units on a scale STANDARD_DEVIATION 11.4232 | 54.666 units on a scale STANDARD_DEVIATION 14.5222 | 57.8 units on a scale STANDARD_DEVIATION 12.67 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 73 | 0 / 40 |
| other Total, other adverse events | 39 / 73 | 12 / 40 |
| serious Total, serious adverse events | 30 / 73 | 3 / 40 |
Outcome results
Primary
Absolute Change in SGRQ Score at 6 Months
Change in SGRQ score - St. George Respiratory Questionnaire from 0 to 100, higher score indicating more limitations (worse), increase in score indicating worse outcome, decrease in score indicating improvement
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Endobronchial Coils | Absolute Change in SGRQ Score at 6 Months | -8.561 score on a scale | Standard Deviation 14.6834 |
| Control | Absolute Change in SGRQ Score at 6 Months | 2.080 score on a scale | Standard Deviation 9.8483 |
Comparison: Study was terminated early, and Statistical Analysis plan was updated to include descriptive statistics only.
Primary
Percent Change in FEV1 at 6 Months
Percent change in FEV1
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Endobronchial Coils | Percent Change in FEV1 at 6 Months | 12.745 percent change from baseline | Standard Deviation 33.1782 |
| Control | Percent Change in FEV1 at 6 Months | -2.604 percent change from baseline | Standard Deviation 10.1628 |
Comparison: Study was closed early in all regions except for France. Statistical Analysis plan was updated to include descriptive statistics only. Sites in France remain open and all subjects in France will be followed through 36 months.
Post Hoc
36 Month Follow Up Visit Completion for French Participants (N=46)
Number of French participants who received treatment with Endobronchial Coil System (randomized and crossover participants) that completed the 36 month follow up visit. All control participants who exited after 6 months are excluded for this outcome.
Time frame: 36 months
Population: Global study was terminated early; however, French Authorities required French participants to be followed through 36-months for safety only. Only subjects that received treatment with Endobronchial Coil System (randomized and crossover control participants) are included in this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Endobronchial Coils | 36 Month Follow Up Visit Completion for French Participants (N=46) | 17 participants |
Post Hoc
Crude Mortality for French Participants (N=46)
Number of deaths for French participants through 36 months. All control participants who exited after 6 months are excluded for this outcome.
Time frame: 36 months
Population: Global study was terminated early; however, French Authorities required French participants to be followed through 36-months for safety only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Endobronchial Coils | Crude Mortality for French Participants (N=46) | 5 Participants |
| Control | Crude Mortality for French Participants (N=46) | 0 Participants |