To Improve Lung Function and Symptoms for Emphysema Patients Using Zephyr Valves

Study Overview
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Brief Summary
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To compare the clinical outcomes of Endoscopic Lung Volume Reduction (ELVR) using Pulmonx Zephyr Valves vs. Standard of Care (SoC) in the treatment of heterogeneous emphysema subjects in a controlled trial design setting.

Official Title
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A Multi-center, Prospective, Randomized, Controlled Trial of Endobronchial Valve Therapy vs. Standard of Care in Heterogeneous Emphysema

Conditions
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COPD, Heterogeneous Emphysema

Intervention / Treatment
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* Device: ELVR (Endoscopic Lung Volume Reduction) with Zephyr Valves


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obtained informed consent. Diagnosis of heterogeneous emphysema with a heterogeneity index of ≥10 % between target and adjacent lobes. Subjects of both genders of at least 40 years of age. 15 % predicted ≤ FEV1≤ 45% predicted. TLC > 100% and RV ≥ 180% predicted. 150 meters < 6MWD < 450 meters. Non-smoker >8 weeks prior to signing the Informed Consent. CV negative target lobe. Additional inclusion criterion French CIP*: - If treated in France, Subject must be entitled to French social security Exclusion Criteria: Any contraindication for bronchoscopic procedure. Evidence of active pulmonary infection. History of 2 or more exacerbations requiring hospitalization over the past 12 months. Known pulmonary hypertension that according to the physician will be unsuitable for EBV treatment. Myocardial infarction or other relevant cardiovascular events in the past 6 months. Significant bronchiectasis seen at CT scan. Greater than two tablespoons of sputum production per day. Prior LVR or LVRS procedure. Criterion 8 French CIP wording*: Prior lung transplant, median sternotomy, LVR or LVRS procedure (including lobectomy). Pulmonary nodule requiring follow-up within any lobe. Pregnant or nursing women. French CIP wording*: Subject is pregnant or lactating, or plans to become pregnant within the study timeframe. Hypercapnia (paCO2 > 7.33 kPa). Current diagnosis of asthma. > 25mg Prednisolon (or equivalent) use/days. Any other condition that as judged by the investigator may make follow-up or investigations inappropriate. Evidence of pleural adhesions or earlier pulmonary surgery. Severe Bullous Emphysema (> 1/3 Hemithorax) Any subject that according to the Declaration of Helsinki is unsuitable for enrollment. Additional exclusion criteria in the French CIP*: History of allergy to silicone and/or nitinol. If treated in France, Subject is a personne vulnerable as defined by French regulation. Simultaneous participation in another drug and/or medical device related clinical.

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: Endoscopic Lung Volume Reduction<br>Patients are implanted with Zephyr Valves | Device: ELVR (Endoscopic Lung Volume Reduction) with Zephyr Valves<br> <br> |
| No Intervention: Standard of Care<br>Patients are given Standard Medical Care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1-second (FEV1) - Responders | The percentage of trial participants in the EBV treatment arm meeting the minimally clinically important difference (MCID) of >12% improved forced expiratory volume in one second (FEV1), obtained immediately following bronchodilator therapy, as compared to the percentage in the control arm at 3 months post-procedure. | Between baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| St George's Respiratory Questionnaire (SGRQ) - Absolute change | Absolute change in the SGRQ in the EBV treatment arm at 3, 6, 12, 18 and 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months. 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. | Between Baseline and 3, 6, 12, 18 and 24 months | 
| St George's Respiratory Questionnaire (SGRQ) - Percent change | Percent change in the SGRQ in the EBV treatment arm at 3, 6, 12, 18 and 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months. 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. | Between Baseline and 3, 6, 12, 18 and 24 months | 
| St George's Respiratory Questionnaire (SGRQ) - Responders | Percentage of subject achieving the MCID for SGRQ in the EBV treatment arm at 3, 6, 12, 18 and 24 months, compared to SoC at 3, 6 and 12 months. 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. | Between Baseline and 3, 6, 12, 18 and 24 months | 
| 6-minute walk distance (6MWT) - Absolute change | Absolute change in 6MWD in the EBV treatment arm at 3, 6, 12, 18, 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months. | Between Baseline and 3, 6, 12, 18, 24 months | 
| 6-minute walk distance (6MWT) - Percent change | Percent change in 6MWD in the EBV treatment arm at 3, 6, 12, 18, 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months. | Between Baseline and 3, 6, 12, 18, 24 months | 
| 6-minute walk distance (6MWT) - Responders | Percentage of subject achieving the MCID for 6MWD in the EBV treatment arm at 3, 6, 12, 18 and 24 months, compared to SoC at 3, 6 and 12 months. | Between Baseline and 3, 6, 12, 18, 24 months | 
| Forced Expiratory Volume in 1-second (FEV1) - Absolute change | Absolute change in FEV1 in the EBV treatment arm at 3, 6, 12, 18, 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months. | Between Baseline and 3, 6, 12, 18, 24 months | 
| Forced Expiratory Volume in 1-second (FEV1) - Percent change | Percentage of subject achieving the MCID for FEV1 in the EBV treatment arm at 6, 12, 18 and 24 months, compared to SoC at 6 and 12 months. | Between Baseline and 6, 12, 18 and 24 months | 
| Forced Expiratory Volume in 1-second (FEV1) - Responders | Absolute change in FEV1 in the EBV treatment arm at 3, 6, 12, 18, 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months. | Between Baseline and 3, 6, 12, 18, 24 months | 
| mMRC (Modified Medical Research Council) score - Responders | Percentage of subject in the EBV treatment arm achieving the MCID for the Modified Scale Research Council Dyspnea Score (mMRC) at 3, 6, 12, 18 and 24 months and the difference between the two arms at 3, 6 and 12 months. 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. | Between Baseline and 3, 6, 12, 18 and 24 months | 
| Target Lobar Volume Reduction (TLVR) - Absolute change | Absolute change in target lobe volume at 45 days in the EBV treatment arm relative to Baseline as assessed by quantitative HRCT analysis (TLVR: Target Lobar Volume Reduction). | Between baseline and 45 days | 
| Target Lobar Volume Reduction (TLVR) - Percent change | Percent change in target lobe volume at 45 days in the EBV treatment arm relative to Baseline as assessed by quantitative HRCT analysis (TLVR: Target Lobar Volume Reduction). | Between baseline and 45 days | 
| Target Lobar Volume Reduction (TLVR) - Responders | Percentage of subjects in EBV arm with a TLVR > 350ml at 45 days relative to baseline. | Between baseline and 45 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endoscopic lung volume reduction, Endobronchial valves