Clinical Study of the RheOx Bronchial Rheoplasty System in Treating the Symptoms of Chronic Bronchitis

Study Overview
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Brief Summary
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This is a prospective, randomized, parallel group, double-blind, sham-controlled, multicenter clinical trial following patients to 2 years. The objective is to assess the safety and effectiveness of Bronchial Rheoplasty for the treatment of the symptoms of chronic bronchitis in adult COPD patients with moderate to severe chronic bronchitis. A total of 270 patients will be randomized at up to 40 study centers in the United States, Canada, and Europe.

Official Title
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A Clinical Evaluation of the RheOx Bronchial Rheoplasty System for the Treatment of the Symptoms of Chronic Bronchitis in Adult Patients With COPD

Conditions
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Chronic Bronchitis

Intervention / Treatment
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* Device: RheOx Bronchial Rheoplasty
* Device: Sham Procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is at least 35 years of age. Patient has chronic bronchitis, defined as productive cough for three months in each of two successive years, whereas other causes of productive cough have been ruled out. Patient has a CAT score ≥ 10. Patient has an SGRQ score ≥ 25. Patient's responses to the first two questions of the CAT instrument sum to ≥ 7 points or the sum is 6 points and the patient's total CAT score is > 20 points. Patient has FEV1/FVC < 0.70. Patient has a pre-procedure post-bronchodilator FEV1 percent predicted of ≥ 30%. Patient is receiving guideline directed pharmacotherapy which includes one or more long acting bronchodilator (LAMA, LABA) with or without an inhaled corticosteroid for at least 8 weeks prior to randomization, unless the patient has attempted such therapy within the past 1 year without significant clinical response or had an adverse reaction. Patient has a cigarette smoking history of at least ten pack years. In the opinion of the Primary investigator, patient is able to undergo 2 bronchoscopies under general anesthesia and is able to adhere to the study follow-up schedule Exclusion Criteria: Patient has known unresolved lower respiratory tract infection (e.g., pneumonia, mycobacterium avium-intracellulare infection (MAI), fungus, tuberculosis). Patient has a steroid-dependent condition requiring >10 mg of oral corticosteroid per day. Patient has any implantable electronic device (e.g., pacemaker, cardioverter defibrillator) that cannot be turned off during the procedure. Patient has a history of ventricular tachy-arrhythmia or clinically significant atrial tachyarrhythmia within the past two years, unless the arrhythmia has been treated and/or patient is in regular rhythm during the screening phase. Patient has unresolved lung cancer. Patient has a pulmonary nodule or cavity that in the judgement of the Primary investigator may require intervention during the course of the study. Patient had prior lung surgery, such as lung transplant, LVRS, lobectomy, lung implant/prosthesis, metal airway stent, valves, coils or bullectomy. Prior pneumothorax without lung resection, pleural procedures without surgery, or segmentectomy are acceptable. Patient has emphysema of greater than or equal to 25% as quantified on baseline HRCT scan (low attenuation area less than -950HU) as determined by the CT Core Lab. Patient has asthma based on Global Initiative for Asthma (GINA) criteria. Patient has clinically significant bronchiectasis influencing the patient's clinical symptoms of cough and phlegm. Patient has actively smoked (including tobacco, marijuana, e-cigarettes, vaping, etc.) within the last 6 months. Patient is unable to walk over 225 meters in 6 minutes. Patient has a serious medical condition that, in the Primary investigator's opinion, could compromise patient safety or confound the interpretation of the patient's response to therapy (e.g., congestive heart failure, cardiomyopathy, or myocardial infarction in the past year, renal failure, liver disease cerebrovascular accident within the past 6 months, uncontrolled diabetes (HbA1c >8%), uncontrolled hypertension (diastolic BP >100mmHg) or autoimmune disease requiring treatment with immunosuppressant medications or a disease requiring chemotherapy). Patient has uncontrolled GERD. Patient has known severe pulmonary hypertension. Patient has a known sensitivity to medication required to perform bronchoscopy (i.e., lidocaine, atropine, benzodiazepines). Patient is pregnant, nursing, or planning to get pregnant during study duration. Patient is currently participating in another clinical study involving an investigational product

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel group design randomizing patients in a 2:1 ratio to the treatment vs. sham group. Randomization will be blocked and stratified by site and FEV1 (<50% vs. >/= 50%)
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RheOx Treatment<br> | Device: RheOx Bronchial Rheoplasty<br>* bronchial rheoplasty is a staged procedure wherein pulsed electric fields are delivered to the right lung in the first treatment visit, and then the left lung is treated approximately 1 month later.<br>|
| Sham Comparator: Sham Procedure<br> | Device: Sham Procedure<br>* staged sham procedure wherein bronchoscopy is performed, the catheter is inserted into the right lung, but energy is not delivered; then the same steps are performed in the left lung approximately 1 month later (no energy is delivered to the patient)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COPD Assessment Test (CAT) Score | Mean change from baseline in the COPD Assessment Test (CAT) total score, the total CAT score ranges from 0 to 40, where lower scores represent lower symptom burden | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distal Airway Volume | Change from baseline distal airway volume (DAV) at expiration using HRCT scans | 6 months | 
| COPD Exacerbations | Rate of moderate and severe COPD exacerbations | 12 months | 
| Goblet Cell Hyperplasia | change from baseline in mean goblet cell hyperplasia score as determined from airway biopsy samples; the grading scale ranges from 0 to 3, where lower scores represent less goblet cell hyperplasia | 1 month | 
| Cough Frequency | change from baseline in cough frequency (coughs/hour in a 24-hour recording period) | 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD