Evaluating the Safety and Efficacy of dNerva Lung Denervation System in Patients With COPD
Purpose
The dNerva Lung Denervation System is one-time treatment intended to improve breathing in Chronic Obstructive Pulmonary Disease (COPD) patients on standard medical care. The purpose of this study is to confirm the safety and efficacy of the Nuvaira Lung Denervation System in the treatment of COPD.
Conditions
- COPD
- Chronic Obstructive Pulmonary Disease
Eligibility
- Eligible Ages
- Between 40 Years and 80 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- ≥ 40 and ≤ 80 years of age at the time of consent. - Women of childbearing potential must not be pregnant, evidenced by a negative pregnancy test (blood or urine) pre-treatment, or lactating and agree not to become pregnant for the duration of the study. - Smoking history of at least 10 pack years. - Not smoking or using any other inhaled substance (e.g. cigarettes, vaping, cannabis, pipes) for a minimum of 2 months prior to consent and agrees to not start for the duration of the study. - Resting SpO2 ≥ 89% on room air. - MMRC ≥ 2; CAT score ≥ 10. - Diagnosis of moderate to severe COPD as defined by FEV1/FVC < 70% (post-bronchodilator), 25% ≤ FEV1 ≤ 70% predicted, and PaCO2 < 50 (if FEV1 < 30%). - RV ≥ 175% of predicted and RV/TLC > 55% (post-bronchodilator). - Participant is on standard medical care, defined as a minimum of therapy with LABA/ICS, LAMA/LABA, or LAMA/LABA/ICS for at least 2 months prior to consent. - If subject has participated in a formal pulmonary rehabilitation program recently, program completion must have occurred ≥3 months prior to consent; if in a maintenance program, subject agrees to continue their current program through their 12-month follow-up visit; NOTE: Prior participation in a pulmonary rehabilitation program is not required for inclusion in the study. - Participant is a candidate for bronchoscopy in the opinion of the investigator or per hospital guidelines and is able to discontinue blood thinning medication peri-procedurally. - Participant is able and agrees to complete all protocol required baseline and follow up tests and assessments including taking certain medications (e.g., azithromycin, prednisolone/prednisone).
Exclusion Criteria
- Body Mass Index (BMI) <18 or >32. - Participant has an implantable electronic device and has not received appropriate medical clearance. - Uncontrolled diabetes in the opinion of the investigator. - 4 or more respiratory related hospitalizations within 1 year of consent. - Malignancy treated with radiation or chemotherapy within 1 year of consent. - Participant diagnosed with a dominant non-COPD lung disease, or condition affecting the lungs, which is the main driver of the participant's clinical symptoms (e.g., cystic fibrosis, paradoxical vocal cord motion, eosinophilic granulomatosis with polyangiitis (EGPA), allergic bronchopulmonary aspergillosis, interstitial lung disease or active tuberculosis or Asthma) or has a documented medical history of pneumothorax within 1 year of consent. - Clinically relevant bronchiectasis, defined as > 1/3 cup mucous expectoration daily. - Pre-existing diagnosis of pulmonary hypertension, clinical evidence of pulmonary hypertension (e.g., cardiovascular function impairment including peripheral edema) and mPAP ≥25 mmHg at rest by right heart catheterization (or estimated right ventricular systolic pressure >50 mmHg by echocardiogram if no previous right heart catheterization). - Myocardial infarction within last 6 months, evidence of life-threatening arrhythmias or acute ischemia, pre-existing documented evidence of a LVEF < 40%, stage C or D (ACC/AHA) or Class III or IV (NYHA) congestive heart failure. - Surgical procedure(s) on the stomach, esophagus or pancreas performed ≤2 years of consent, or ongoing related symptoms within the past year. - Symptomatic gastric motility disorder(s) (e.g., gastroparesis) as evidenced by GCSI score ≥18.0, severe uncontrolled GERD (e.g., refractory heartburn, endoscopic esophagitis) or severe dysphagia (e.g., esophageal stricture, achalasia, esophageal spasm). NOTE: Participants with a hiatal hernia are allowed if Participant meets all other enrollment criteria. - Any disease or condition that might interfere with completion of a procedure or this study (e.g., structural esophageal disorder, life expectancy <3 years). - Prior lung or chest procedure (e.g., BLVR explant procedure, median sternotomy, bullectomy, lobectomy, segmentectomy or other interventional lung or chest procedure) performed ≤1 year of consent? Participants with lung transplant, BLVR valves, LVRS, metal stents within 5cm of the anticipated treatment location; presence of lung volume reduction valves, coils or other lung implants. - Daily use of >20 mg of prednisone or its equivalent at the time of consent. - Known contraindication or allergy to medications required for bronchoscopy or general anesthesia (e.g., lidocaine, atropine, propofol, sevoflurane) that cannot be medically controlled. - Baseline chest CT scan reveals bronchial anatomy cannot be treated with available catheter sizes; presence of whole lung emphysema >20% (-950 HU), single lung emphysema >26% (-950 HU), severe bullous disease (>1/3 hemithorax) or discovery of a mass that requires treatment. - Participant is currently enrolled in another drug or interventional clinical trial that has not completed follow-up.
Study Design
- Phase
- N/A
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Participants will be randomized 1:1 into two arms: Targeted Lung Denervation (TLD) therapy plus standard medical care (Treatment) and standard medical care alone (Control). Randomization will be stratified based on investigational site, participation in a pulmonary rehabilitation maintenance program, and baseline single inhaled long acting bronchodilator (LABA-ICS only). Participants randomized to Treatment: will undergo TLD treatment with the dNerva Lung Denervation System while continuing the standard medical care that they were on prior to randomization and followed for 2 years or until study closure, whichever is earlier. Participants randomized to Control: will continue the standard medical care that they were on prior to randomization, followed for 1 year, then given the option to receive TLD treatment. Whether treated or not, participants will continue follow-up for 1 more year or until study closure, whichever is earlier.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Targeted Lung Denervation (TLD) treatment and continue on the same standard COPD medical care |
Targeted Lung Denervation (TLD)Therapy is a bronchoscopically guided minimally invasive one-time treatment using the dNerva Lung Denervation System. Patients will also continue taking their standard of care COPD maintenance medication (at minimum LABA/ICS, LAMA/LABA or LABA/LAMA/ICS) that they were on prior to randomization. |
|
|
No Intervention Continue on the same standard COPD medical care |
Continue taking their same standard of care COPD maintenance medication (at minimum LABA/ICS, LAMA/LABA or LABA/LAMA/ICS) that they were on prior to randomization. |
|
|
Other Targeted Lung Denervation (TLD) crossover treatment after 1-year follow-up for 'No Intervention' Arm |
Participants in 'No Intervention' arm who complete their 1-year follow-up will have the option to receive TLD treatment and will be followed for 1 year after the crossover treatment. |
|
Recruiting Locations
University of Alabama-Birmingham Hospital - UAB Lung Health Center
Birmingham 4049979, Alabama 4829764 35233
Birmingham 4049979, Alabama 4829764 35233
More Details
- Status
- Recruiting
- Sponsor
- Nuvaira, Inc.
Detailed Description
The primary objective of this study is to demonstrate the superiority of treatment with the dNerva Lung Denervation System on top of standard medical care (Treatment arm) compared to standard medical care alone (Control arm) to improve lung function in COPD participants with high RV and low emphysema. The secondary objective is to compare other efficacy assessments between the Treatment arm and the Control arm, and to confirm the safety profile of lung denervation.