Clinical trial NCT02022683: To Improve Lung Function and Symptoms for Emphysema Patients Using Zephyr Valves
Official title: A Multi-center, Prospective, Randomized, Controlled Trial of Endobronchial Valve Therapy vs. Standard of Care in Heterogeneous Emphysema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COPD
Heterogeneous Emphysema
Keywords: Endoscopic lung volume reduction
Endobronchial valves
Lead sponsor: Pulmonx Corporation
Sponsor class: INDUSTRY
First posted: 2013-12-30
Enrollment: 97
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Forced Expiratory Volume in 1-second (FEV1) - Responders
timeFrame: Between baseline and 3 months
Secondary outcomes:
measure: St George's Respiratory Questionnaire (SGRQ) - Absolute change
timeFrame: Between Baseline and 3, 6, 12, 18 and 24 months
measure: St George's Respiratory Questionnaire (SGRQ) - Percent change
timeFrame: Between Baseline and 3, 6, 12, 18 and 24 months
measure: St George's Respiratory Questionnaire (SGRQ) - Responders
timeFrame: Between Baseline and 3, 6, 12, 18 and 24 months
measure: 6-minute walk distance (6MWT) - Absolute change
timeFrame: Between Baseline and 3, 6, 12, 18, 24 months
measure: 6-minute walk distance (6MWT) - Percent change
timeFrame: Between Baseline and 3, 6, 12, 18, 24 months
measure: 6-minute walk distance (6MWT) - Responders
timeFrame: Between Baseline and 3, 6, 12, 18, 24 months
measure: Forced Expiratory Volume in 1-second (FEV1) - Absolute change
timeFrame: Between Baseline and 3, 6, 12, 18, 24 months
measure: Forced Expiratory Volume in 1-second (FEV1) - Percent change
timeFrame: Between Baseline and 6, 12, 18 and 24 months
measure: Forced Expiratory Volume in 1-second (FEV1) - Responders
timeFrame: Between Baseline and 3, 6, 12, 18, 24 months
measure: mMRC (Modified Medical Research Council) score - Responders
timeFrame: Between Baseline and 3, 6, 12, 18 and 24 months
measure: Target Lobar Volume Reduction (TLVR) - Absolute change
timeFrame: Between baseline and 45 days
measure: Target Lobar Volume Reduction (TLVR) - Percent change
timeFrame: Between baseline and 45 days
measure: Target Lobar Volume Reduction (TLVR) - Responders
timeFrame: Between baseline and 45 days
Other outcomes:
measure: Adverse Events
timeFrame: Between baseline and 24 months
measure: PaO2 - Absolute change
timeFrame: Between baseline and 3 months
measure: PaO2 - Percent change
timeFrame: Between baseline and 3 months
measure: Residual Volume (RV) - Absolute change
timeFrame: Between Baseline and 3, 6 and 12, 18 and 24 months
measure: Residual Volume (RV) - Percent change
timeFrame: Between Baseline and 3, 6 and 12, 18 and 24 months
measure: EQ-5D Summary Index - Absolute change
timeFrame: Between Baseline and 3, 6, 12, 18 and 24 months
measure: EQ-5D Summary Index Percent change
timeFrame: Between Baseline and 3, 6, 12, 18 and 24 months
measure: Mean number of additional hospitalizations and/or visits caused by respiratory conditions
timeFrame: Between baseline and 24 months
Locations:
city: Gent
country: Belgium
facility: Universiteit Gent
city: Menen
country: Belgium
facility: AZ Delta
city: Grenoble
country: France
facility: CHU
city: Nice
country: France
facility: CHU Hôpital Pasteur
city: Paris
country: France
facility: Groupe Hospitalier Pitié Salpétrière
city: Paris
country: France
facility: Hôpital Bichat Claude Bernard
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum
city: Essen
country: Germany
facility: Ruhrlandklinik Westdeutsches Lungenzentrum
city: Heidelberg
country: Germany
facility: Thoraxklinik am Universitäts Klinikum Heidelberg
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Lund
country: Sweden
facility: Skane University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Sutton in Ashfield
country: United Kingdom
facility: Sherwood Forest Hospitals NHS
state: Nottinghamshire
city: Clydebank
country: United Kingdom
facility: West of Scotland Regional Heart & Lung Centre - Golden Jubilee National Hospital
state: West Dunbartonshire Scotland
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: London
country: United Kingdom
facility: The Royal Brompton Hospital & Harefield NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
Study officials:
affiliation: Uppsala University Hospital, Sweden
name: Gunnar Hillerdal, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kemp SV, Slebos DJ, Kirk A, Kornaszewska M, Carron K, Ek L, Broman G, Hillerdal G, Mal H, Pison C, Briault A, Downer N, Darwiche K, Rao J, Hubner RH, Ruwwe-Glosenkamp C, Trosini-Desert V, Eberhardt R, Herth FJ, Derom E, Malfait T, Shah PL, Garner JL, Ten Hacken NH, Fallouh H, Leroy S, Marquette CH; TRANSFORM Study Team *. A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (TRANSFORM). Am J Respir Crit Care Med. 2017 Dec 15;196(12):1535-1543. doi: 10.1164/rccm.201707-1327OC.