Pulmonx Endobronchial Valves Used in Treatment of Emphysema (LIBERATE Study)

Study Overview
=================
Brief Summary
-----------------
The purpose of this research is to study an investigational medical device that is designed to produce lung volume reduction in diseased areas of the lungs in patients with severe emphysema.

Detailed Description
-----------------
The Pulmonx Zephyr Endobronchial Valve (EBV) is an implantable bronchial valve intended to decrease volume in targeted regions of the lung. It is indicated for the treatment of patients with severe emphysema. The EBV are placed in the diseased region of the lung using bronchoscopy. Bronchoscopy is a way to access the lungs using a small tube with a camera on the end. As the diseased region of the lung shrinks in size, healthier regions may expand and function more efficiently, resulting in improved breathing. The LIBERATE Study is a clinical trial with two groups. Participants are assigned at random to the 'Treatment' group or to the 'Control' group. The 'Treatment' group will receive the Zephyr Endobronchial Valve (EBV) in combination with optimal medical therapy. The 'Control' group will receive optimal medical therapy alone. For every three participants in the study, two will go into the 'Treatment' group and one will go into the 'Control' group. It is hypothesized that after placement of the EBV, lung function will be improved as compared to standard medical therapy alone. Based on the 12-month follow up data from the LIBERATE Study, the Zephyr Endobronchial Valve System was approved by the FDA for the treatment of severe emphysema in June 2018. Following this PMA approval, and in agreement with the FDA, the ongoing long term follow-up (out to 5 years) of patients in the LIBERATE Study will now be conducted as a Post-approval study under the auspices of the LIBERATE Extension Study. This is an administrative change with absolutely no change to the design or conduct of the study and, therefore has no material impact to the study participants or the study sites. All annual follow-up visits and evaluations are per the original LIBERATE Study protocol. Reporting to the FDA will be as the LIBERATE Extension Study.

Official Title
-----------------
Lung Function Improvement After Bronchoscopic Lung Volume Reduction With Pulmonx Endobronchial Valves Used in Treatment of Emphysema

Conditions
-----------------
Emphysema

Intervention / Treatment
-----------------
* Device: EBV
* Other: Optimal Medical Management


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical and radiological evidence of emphysema Nonsmoking for 4 months prior to screening interview BMI less than 35 kg/m2 Stable on current medication regimen Forced expiratory volume in one second (FEV1) between 15% and 45% of predicted value Residual Volume less than 175% predicted (determined by body plethysmography) Little or no collateral ventilation (CV-) as determined using the Chartis System Exclusion Criteria: Had two or more hospitalizations over the last year for a COPD exacerbation Had two or more hospitalizations over the last year for pneumonia Had a prior lung transplant, lung volume reduction surgery, bullectomy or lobectomy Had a heart attack or congestive heart failure within the last 6 months Have heart arrhythmia Is alpha-1 antitrypsin deficient

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EBV and Optimal Medical Management<br>This study arm will undergo EBV treatment along with optimal medical management, including smoking cessation program, pulmonary rehabilitation, usual medications and oxygen supplementation as necessary. | Device: EBV<br>* This study arm will undergo EBV treatment and also receive optimal medical management, including smoking cessation program support, pulmonary rehabilitation, usual medications and oxygen supplementation as necessary.<br>|
| Other: Optimal Medical Management<br>This study arm will receive maximal medical management, including smoking cessation program support if necessary, pulmonary rehabilitation, usual medications and oxygen supplementation as necessary. | Other: Optimal Medical Management<br>* This study arm will receive optimal medical management, including smoking cessation program support, pulmonary rehabilitation, usual medications and oxygen supplementation as necessary.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1-second (FEV1) | The percentage of study participants in the Zephyr Valve EBV (Endobronchial Valves) treatment arm meeting the clinically significant threshold of >15% improved forced expiratory volume in one second (FEV1), obtained immediately following bronchodilator therapy, as compared to the percentage in the control arm at 1 year post-procedure. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 Post-bronchodilator Absolute Change | Difference between study arms in absolute change from baseline for post-bronchodilator FEV1 score at 1 year (value at 1 year minus value at baseline). | 1 year | 
| St. George's Respiratory Questionnaire (SGRQ) | Difference between study arms in 'absolute change from baseline' for SGRQ score at 1 year (value at 1 year minus value at baseline). The St. George's Respiratory Questionnaire measures health status (quality of life) in patients with diseases of airways obstruction. The questionnaire comprises of two parts: Part I: Symptoms (frequency & severity) Part II: Activities that cause or are limited by breathlessness; Impacts (social functioning, psychological disturbances resulting from airways disease) A Total score is calculated which summarizes the impact of the disease on overall health status. Scores range from 0 to 100, with higher scores indicating more limitations. | 1 year | 
| 6-minute Walk Distance | Difference between study arms in 'absolute and percentage change from baseline' for 6MWD at 1 year (value at 1 year minus value at baseline). | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
emphysema, endobronchial valve, treatments, pulmonary rehabilitation, lung volume reduction