Targeted Lung Denervation for Patients With Moderate to Severe COPD

Study Overview
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Brief Summary
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The purpose of this study is to evaluate safety of Targeted Lung Denervation (or TLD) in patients suffering from moderate to severe COPD. It is hypothesized that TLD will have a similar safety profile and improved physiological and functional outcomes to a sham-control.

Detailed Description
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A prospective, sequential two phase multicenter, randomized double-blind, safety, & feasibility study. The goal of AIRFLOW-1 will be to compare two energy doses and select the optimal energy dose to be utilized in AIRFLOW-2. The goal of AIRFLOW-2 is to compare the optimal energy dose to a sham control. All subjects will be followed for a minimum of 3 years.

Official Title
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A Sequential Two Phase Multicenter, Randomized Study to Optimize Dose Selection and Evaluate Safety After Treatment With the Holaira™ Lung Denervation System in Patients With Moderate to Severe COPD.

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Device: Holaira™ Lung Denervation System with energy delivery
* Device: Holaira™ Lung Denervation System without energy delivery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of COPD with 30% ≤ FEV1 < 60% and FEV1/FVC <70% (post-bronchodilator); Patient ≥ 40 and ≤ 75 years of age at the time of consent; The patient has no child bearing potential or a negative pregnancy test (serum or urine), if applicable; Smoking history of at least 10 pack years; Non-smoking for a minimum of 2 months prior to consent and agrees to continue not smoking for the duration of the study; Participated in a pulmonary rehabilitation program or engaged in regular physical activity under professional supervision in the past 12 months; Exclusion Criteria: Has been less than 6 weeks following the resolution of a COPD exacerbation or active lower respiratory infection (eg. pneumonia); History of recurrent respiratory infections and/or COPD exacerbations (more than 2 hospitalizations within 1 year of enrollment); Prior lung or chest procedure (eg. lung transplant, LVRS, BLVR, lung implant, metal stent, valves, coils, median sternotomy, bullectomy, segmentectomy, or lobectomy); Documented history of asthma diagnosed with onset <30 years of age, cystic fibrosis, paradoxical vocal cord motion, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, severe interstitial lung disease or active tuberculosis; Pulmonary nodule requiring follow-up or intervention unless proven benign; Daily use of >10 mg of prednisone or its equivalent at the time of enrollment;

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Targeted Lung Denervation<br>active targeted lung denervation | Device: Holaira™ Lung Denervation System with energy delivery<br> <br> |
| Sham Comparator: Sham-Control<br>non-active targeted lung denervation | Device: Holaira™ Lung Denervation System without energy delivery<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AIRFLOW-1: Therapeutic interventions through 3 months; AIRFLOW-2: and rate of respiratory adverse events between 3 and 6.5 months | Respiratory adverse events is defined as: worsening bronchitis, worsening dyspnea, common cold, COPD exacerbation, influenza, pneumonia, respiratory infection, respiratory failure, tachypnea and wheezing. Subjects may have reported more than one type of respiratory adverse event. | 3-6.5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events over 3 years | The assessment of safety will be based on reporting of adverse events, particularly those adverse events that are respiratory in origin. | 3 years | 
| Device Success | Device success is defined as ability to deliver the test device to its intended locations, provide complete circumferential treatment and removal of the test device without the report of an adverse event during the procedure. | 6 months | 
| Spirometry measures | Measures include: FEV1, FVC, FEV1/FVC | 3 years | 
| Change in Functional testing: Cycle Ergometry & 6MWT |  | 3 years | 
| Heath-related Quality of Life (SGRQ-C & EQ-5D) |  | 3 years | 
| Procedure Success | Procedure Success is defined as device success without the report of an adverse event through hospital discharge. | Through discharge | 
| Plethysmography measures | Measures include Raw, TLC, IC, ITGW | 3 years | 
| CT Scan assessment |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Targeted Lung Denervation, Intervention, Lung Function, Safety, Device