Improving Patient Outcomes by Selective Implantation of the Zephyr EBV - Study

Study Overview
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Brief Summary
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The aim of this prospective, randomized, controlled, one-way crossover study is to assess and compare the efficacy of the Zephyr endobronchial valves vs. Standard of Care (SoC) in patients suffering from COPD with Homogeneous Emphysema. Patients will be followed up for 12 months after randomization. Patients in the SoC arm will crossover to the EBV treatment arm after the 6-month visit and will be followed up for 6 additional months.The primary objective is the variation of FEV1 between baseline and 3-month follow-up visit. The secondary objectives will evaluate quality of life, exercise capacity, dyspnea (including BODE index) changes, target lobe volume reduction, as well as safety outcomes.

Official Title
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A Multicentre, Prospective, Randomized, Controlled, One-way Crossover Investigation of Endobronchial Valve (EBV) Therapy vs. Standard of Care (SoC) in Homogeneous Emphysema

Conditions
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COPD Patients With Homogeneous Emphysema, Endoscopic Lung Volume Reduction With Endobronchial Valve

Intervention / Treatment
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* Device: Endobronchial Valve


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Homogeneous emphysema 15% ≤ FEV1 ≤ 45% predicted TLC > 100% predicted RV ≥ 200% predicted 6MWT ≥ 150 m Non-smoker > 8 weeks prior to study entry Absence of Collateral Ventilation in the target lobe Exclusion Criteria: Active pulmonary infection More than 3 exacerbations with hospitalizations over the past 12 months Pulmonary hypertension (sPAP > 45 mmHg) MI or other relevant CV events in the past 6 months Alpha-1 antitrypsin deficiency Bronchiectasis Prior LVR or LVRS procedure > 20% difference in perfusion between right and left lung Hypercapnia (paCO2 > 55 mmHg Asthma Use of more than 25 mg/day prednisolone or equivalent Severe bullous emphysema Systemic or malignant disease with high death probability within 12 months

Ages Eligible for Study
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Minimum Age: 40 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ELVR with Endobronchial Valves<br>Endoscopic Lung Volume Reduction with Zephyr Endobronchial Valve | Device: Endobronchial Valve<br>* Endoscopic Lung Volume Reduction with Zephyr Endobronchial Valve<br>|
| No Intervention: Standard of Care<br>Patients will receive optimal drug therapy and medical management according to clinical practice. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Forced Expiratory Volume in 1 s (FEV1) (ITT Population) | Percentage change in FEV1 at 3 months relative to Baseline in the EBV group, compared to the SoC group. | At baseline and after 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Target Lobe Volume for EBV Group (ITT Population) | Target Lobe Volume Reduction (TLVR) was evaluated by quantitative analysis of HRCT scans at Baseline and at 3-months post-valve placement to measure the target lobe volume. | At baseline and after 3 months | 
| Percent Change in Target Lobe Volume for EBV Group (ITT Population) | Target Lobe Volume Reduction (TLVR) was evaluated by quantitative analysis of HRCT scans at Baseline and at 3-months post-valve placement to measure the target lobe volume. | At baseline and after 3 months | 
| Percent of Subjects in the EBV Group With a Target Lobe Volume Reduction (TLVR) of ≥ 350ml at 3 Months | The threshold of TLVR ≥350 mL was used to determine the proportion of subjects that achieved this amount of TLVR in the EBV group. | At baseline and after 3 months | 
| Absolute Change in FEV1 (L) Post Bronchodilator at 3 Months | The mean absolute change in FEV1(L) relative to Baseline at 3 months between the EBV and SoC groups | At baseline and after 3 months | 
| Absolute Change in FEV1 (% Predicted) Post Bronchodilator at 3 Months | The mean absolute change in FEV1(% Predicted) relative to Baseline at 3 months between the EBV and SoC groups | At baseline and after 3 months | 
| Absolute Change in Residual Volume (RV) at 3 Months | Mean absolute change in Residual Volume relative to Baseline at 3 months between the EBV and SoC groups | At baseline and after 3 months | 
| Percent Change in Residual Volume (RV) at 3 Months | Mean percent change in Residual Volume relative to Baseline at 3 months between the EBV and SoC groups | At baseline and after 3 months | 
| Percent Predicted Change in Residual Volume at 3 Months | Percent predicted change in RV relative to Baseline at 3 months between the EBV and SoC groups | At baseline and after 3 months | 
| Absolute Change in Six-Minute Walk Distance at 3 Months | Mean absolute change in the 6MWD from Baseline to 3 months in the EBV group compared to the SOC | At baseline and after 3 months | 
| Percent Change in Six-Minute Walk Distance at 3 Months | Mean percent change in the 6MWD from Baseline to 3 months in the EBV group compared to the SOC | At baseline and after 3 months | 
| Absolute Change in the SGRQ Total Score From Baseline to 3 Months | Mean absolute change in the St. George's Respiratory Questionnaire Total Score from Baseline to 3 months in the EBV group compared to the SoC group. Scores range from 0 to 100, with higher scores indicating more limitations. | At baseline and after 3 months | 
| Percent Change (%) in the SGRQ Total Score From Baseline to 3 Months | Mean percent change in the SGRQ Total Score from Baseline to 3 months in the EBV group compared to the SoC group | At baseline and after 3 months | 
| Absolute Change in the mMRC Dyspnea Score From Baseline to 3 Months | Mean absolute change in the Modified Medical Research Council (mMRC) Dyspnea Score from Baseline to 3 months in the EBV group compared to the SoC group. The mMRC (Modified Medical Research Council) stratifies severity of dyspnea in respiratory diseases. The severity of dyspnea is rated on a scale of 0 to 4, with higher scores indicating more limitations. | At baseline and after 3 months | 
| Percent Change (%) in the mMRC Dyspnea Score From Baseline to 3 Months | Mean percent change in the mMRC Dyspnea Score from Baseline to 3 months in the EBV group compared to the SoC group. The mMRC (Modified Medical Research Council) stratifies severity of dyspnea in respiratory diseases. The severity of dyspnea is rated on a scale of 0 to 4, with higher scores indicating more limitations. | At baseline and after 3 months | 
| Absolute Change in the CAT Total Score From Baseline to 3 Months | Mean absolute change in the COPD Assessment Test (CAT) Total Score from Baseline to 3 months in the EBV group compared to the SoC group. The COPD Assessment Test (CAT) is an eight-item questionnaire designed to quantify the impact of COPD symptoms on the health status of patients. The CAT provides a score of 0-40 to indicate the impact of disease. | At baseline and after 3 months | 
| Percent Change (%) in CAT Total Score From Baseline to 3 Months | The COPD Assessment Test (CAT) is an eight-item questionnaire designed to quantify the impact of COPD symptoms on the health status of patients. The CAT provides a score of 0-40 to indicate the impact of disease. Higher scores denote a more severe impact of COPD on a patient's life. | At baseline and after 3 months | 
| Absolute Change in EQ-5D Summary Index From Baseline to 3 Months | Mean absolute change in the EQ-5D Summary Index from Baseline to 3 months in the EBV group compared to the SoC group. EQ-5D is a standardized instrument to measure health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ VAS. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D health states may be converted into a single summary index by applying a formula that attaches weights to each of the levels in each dimension. The maximum score of 1 indicates the best health state, while 0 indicates the worst health state. | At baseline and after 3 months | 
| Percent Change (%) in EQ-5D Summary Index From Baseline to 3 Months | Mean percent change in EQ-5D Summary Index from Baseline to 3 months in the EBV group compared to the SoC group. | At baseline and after 3 months | 
| Absolute Change in EQ-5D VAS (Health State Today) Score From Baseline to 3 Months | Mean absolute change in the EQ-5D VAS (Health State Today) Score from Baseline to 3 months in the EBV group compared to the SoC group. Scores range from 0 to 100, with higher scores indicating better outcome. | At baseline and after 3 months |