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

Not Applicable

Completed

• Conditions: COPD; Heterogeneous Emphysema
• Interventions: Device: ELVR (Endoscopic Lung Volume Reduction) with Zephyr Valves

• Registration Number: NCT02022683
• Lead Sponsor: Pulmonx Corporation

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-12-17
• Study First Submitted QC: 2013-12-21
• Study First Posted: 2013-12-30
• Study Start: 2014-01-28
• Primary Completion: 2017-01-20
• Study Completion: 2018-09-27
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-28
• Last Update Posted: 2019-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 97

Inclusion Criteria

1. Obtained informed consent.
2. Diagnosis of heterogeneous emphysema with a heterogeneity index of ≥10 % between target and adjacent lobes.
3. Subjects of both genders of at least 40 years of age.
4. 15 % predicted ≤ FEV1≤ 45% predicted.
5. TLC > 100% and RV ≥ 180% predicted.
6. 150 meters < 6MWD < 450 meters.
7. Non-smoker >8 weeks prior to signing the Informed Consent.
8. CV negative target lobe.

Additional inclusion criterion French CIP*:

• If treated in France, Subject must be entitled to French social security

Exclusion Criteria

1. Any contraindication for bronchoscopic procedure.
2. Evidence of active pulmonary infection.
3. History of 2 or more exacerbations requiring hospitalization over the past 12 months.
4. Known pulmonary hypertension that according to the physician will be unsuitable for EBV treatment.
5. Myocardial infarction or other relevant cardiovascular events in the past 6 months.
6. Significant bronchiectasis seen at CT scan.
7. Greater than two tablespoons of sputum production per day.
8. Prior LVR or LVRS procedure. Criterion 8 French CIP wording*: Prior lung transplant, median sternotomy, LVR or LVRS procedure (including lobectomy).
9. Pulmonary nodule requiring follow-up within any lobe.
10. Pregnant or nursing women. French CIP wording*: Subject is pregnant or lactating, or plans to become pregnant within the study timeframe.
11. Hypercapnia (paCO2 > 7.33 kPa).
12. Current diagnosis of asthma.
13. > 25mg Prednisolon (or equivalent) use/days.
14. Any other condition that as judged by the investigator may make follow-up or investigations inappropriate.
15. Evidence of pleural adhesions or earlier pulmonary surgery.
16. Severe Bullous Emphysema (> 1/3 Hemithorax)
17. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Endoscopic Lung Volume Reduction	ELVR (Endoscopic Lung Volume Reduction) with Zephyr Valves	Patients are implanted with Zephyr Valves

Primary Outcome Measures

Name	Time	Method
Forced Expiratory Volume in 1-second (FEV1) - Responders	Between baseline and 3 months	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.

Secondary Outcome Measures

Name	Time	Method
St George's Respiratory Questionnaire (SGRQ) - Absolute change	Between Baseline and 3, 6, 12, 18 and 24 months	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.
Forced Expiratory Volume in 1-second (FEV1) - Responders	Between Baseline and 3, 6, 12, 18, 24 months	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.
St George's Respiratory Questionnaire (SGRQ) - Percent change	Between Baseline and 3, 6, 12, 18 and 24 months	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.
6-minute walk distance (6MWT) - Absolute change	Between Baseline and 3, 6, 12, 18, 24 months	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.
6-minute walk distance (6MWT) - Responders	Between Baseline and 3, 6, 12, 18, 24 months	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.
St George's Respiratory Questionnaire (SGRQ) - Responders	Between Baseline and 3, 6, 12, 18 and 24 months	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.
6-minute walk distance (6MWT) - Percent change	Between Baseline and 3, 6, 12, 18, 24 months	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.
Forced Expiratory Volume in 1-second (FEV1) - Absolute change	Between Baseline and 3, 6, 12, 18, 24 months	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.
Forced Expiratory Volume in 1-second (FEV1) - Percent change	Between Baseline and 6, 12, 18 and 24 months	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.
mMRC (Modified Medical Research Council) score - Responders	Between Baseline and 3, 6, 12, 18 and 24 months	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.
Target Lobar Volume Reduction (TLVR) - Absolute change	Between baseline and 45 days	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).
Target Lobar Volume Reduction (TLVR) - Responders	Between baseline and 45 days	Percentage of subjects in EBV arm with a TLVR \> 350ml at 45 days relative to baseline.
Target Lobar Volume Reduction (TLVR) - Percent change	Between baseline and 45 days	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).

Trial Locations

Locations (17)

Hôpital Bichat Claude Bernard; 🇫🇷 Paris, France

Universiteit Gent; 🇧🇪 Gent, Belgium

Skane University Hospital; 🇸🇪 Lund, Sweden

AZ Delta; 🇧🇪 Menen, Belgium

Charité Campus Virchow-Klinikum; 🇩🇪 Berlin, Germany

Ruhrlandklinik Westdeutsches Lungenzentrum; 🇩🇪 Essen, Germany

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands

Uppsala University Hospital; 🇸🇪 Uppsala, Sweden

Sherwood Forest Hospitals NHS; 🇬🇧 Sutton in Ashfield, Nottinghamshire, United Kingdom

West of Scotland Regional Heart & Lung Centre - Golden Jubilee National Hospital; 🇬🇧 Clydebank, West Dunbartonshire Scotland, United Kingdom

University Hospital of Wales; 🇬🇧 Cardiff, United Kingdom

Sheffield Teaching Hospitals NHS Foundation Trust; 🇬🇧 Sheffield, United Kingdom

The Royal Brompton Hospital & Harefield NHS Foundation Trust; 🇬🇧 London, United Kingdom

CHU Hôpital Pasteur; 🇫🇷 Nice, France

CHU; 🇫🇷 Grenoble, France

Thoraxklinik am Universitäts Klinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Groupe Hospitalier Pitié Salpétrière; 🇫🇷 Paris, France