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

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

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.

Study Overview

• Status: Completed
• Conditions: COPD; Heterogeneous Emphysema
• Intervention / Treatment: Device: ELVR (Endoscopic Lung Volume Reduction) with Zephyr Valves

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Universiteit Gent
  • Menen, Belgium, 8930
    • AZ Delta
• France
  • Grenoble, France, 38043
    • CHU
  • Nice, France, 06002
    • CHU Hopital Pasteur
  • Paris, France, 75013
    • Groupe Hospitalier Pitie Salpetriere
  • Paris, France, 75877
    • Hopital Bichat Claude Bernard
• Germany
  • Berlin, Germany, 13353
    • Charité Campus Virchow-Klinikum
  • Essen, Germany, 45239
    • Ruhrlandklinik Westdeutsches Lungenzentrum
  • Heidelberg, Germany, 69126
    • Thoraxklinik am Universitats klinikum Heidelberg
• Netherlands
  • Groningen, Netherlands, 9700
    • University Medical Center Groningen
• Sweden
  • Lund, Sweden, 221 85
    • Skane University Hospital
  • Uppsala, Sweden, 751 85
    • Uppsala University Hospital
• United Kingdom
  • Cardiff, United Kingdom, CF144XW
    • University Hospital of Wales
  • London, United Kingdom, SW3 6NP
    • The Royal Brompton Hospital & Harefield NHS Foundation Trust
  • Sheffield, United Kingdom, S5 7AU
    • Sheffield Teaching Hospitals NHS Foundation Trust
  • Nottinghamshire
    • Sutton in Ashfield, Nottinghamshire, United Kingdom, NG17 4JL
      • Sherwood Forest Hospitals NHS
  • West Dunbartonshire Scotland
    • Clydebank, West Dunbartonshire Scotland, United Kingdom, G81 4DY
      • West of Scotland Regional Heart & Lung Centre - Golden Jubilee National Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endoscopic Lung Volume Reduction; Patients are implanted with Zephyr Valves	Device: ELVR (Endoscopic Lung Volume Reduction) with Zephyr Valves
No Intervention: Standard of Care; Patients are given Standard Medical Care

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Adverse events (condition/procedure related AE's, SAE's, ADE's and SADE's) occurring up to 24 months post EBV placement and up to 12 months post randomization (for any remaining subjects in the SoC group).	Between baseline and 24 months
PaO2 - Absolute change	Absolute change in PaO2 in the EBV treatment arm at 3 months relative to Baseline.	Between baseline and 3 months
PaO2 - Percent change	Percent change in PaO2 in the EBV treatment arm at 3 months relative to Baseline.	Between baseline and 3 months
Residual Volume (RV) - Absolute change	Absolute change in residual volume (RV) in the EBV treatment arm at 3, 6 and 12, 18 and 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.	Between Baseline and 3, 6 and 12, 18 and 24 months
Residual Volume (RV) - Percent change	Percent change in residual volume (RV) in the EBV treatment arm at 3, 6 and 12, 18 and 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.	Between Baseline and 3, 6 and 12, 18 and 24 months
EQ-5D Summary Index - Absolute change	Absolute change relative to Baseline in the EBV treatment arm at 3, 6, 12, 18 and 24 months of the EQ-5D Summary Index and the difference between the two arms at, 3, 6 and 12 months. EQ-5D is a standardized instrument used to measure health-related quality of life for 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 VAS records the patient's self-rated health on a vertical visual analogue scale. This can be used as a quantitative measure of health outcome that reflects the patient's own judgement. The scores on these five dimensions can be presented as a health profile or can be converted to a single summary index number (utility) reflecting preferability compared to other health profiles.	Between Baseline and 3, 6, 12, 18 and 24 months
EQ-5D Summary Index Percent change	Percent change relative to Baseline in the EBV treatment arm at 3, 6, 12, 18 and 24 months of the EQ-5D Summary Index and the difference between the two arms at, 3, 6 and 12 months. EQ-5D is a standardized instrument used to measure health-related quality of life for 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 VAS records the patient's self-rated health on a vertical visual analogue scale. This can be used as a quantitative measure of health outcome that reflects the patient's own judgement. The scores on these five dimensions can be presented as a health profile or can be converted to a single summary index number (utility) reflecting preferability compared to other health profiles.	Between Baseline and 3, 6, 12, 18 and 24 months
Mean number of additional hospitalizations and/or visits caused by respiratory conditions	The mean number of visits (Number of participants reporting visits/total number of visits) caused by respiratory conditions during the study period will be recorded for health economical purposes in both treatment and control subjects.	Between baseline and 24 months

Collaborators and Investigators

• Sponsor: Pulmonx Corporation
• Investigators: Principal Investigator: Gunnar Hillerdal, MD, PhD, Uppsala University Hospital, Sweden

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2014
• Primary Completion (Actual): January 20, 2017
• Study Completion (Actual): September 27, 2018

Study Registration Dates

• First Submitted: December 17, 2013
• First Submitted That Met QC Criteria: December 21, 2013
• First Posted (Estimate): December 30, 2013

Study Record Updates

• Last Update Posted (Actual): July 2, 2019
• Last Update Submitted That Met QC Criteria: June 28, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Endobronchial valves; Endoscopic lung volume reduction
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Emphysema
• Other Study ID Numbers: 630-0015/A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No