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

COPD Clinical Trial

— TRANSFORM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02022683
• Other study ID #: 630-0015/A
• Status: Completed
• Phase: N/A
• Start date: January 28, 2014
• Est. completion date: September 27, 2018

Study information

• Verified date: June 2019
• Source: Pulmonx, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: September 27, 2018
• Est. primary completion date: January 20, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COPD
• Emphysema
• Heterogeneous Emphysema
• Pulmonary Emphysema

Intervention

Device:
• ELVR (Endoscopic Lung Volume Reduction) with Zephyr Valves

Locations

Country	Name	City	State
Belgium	Universiteit Gent	Gent
Belgium	AZ Delta	Menen
France	CHU	Grenoble
France	CHU Hôpital Pasteur	Nice
France	Groupe Hospitalier Pitié Salpétrière	Paris
France	Hôpital Bichat Claude Bernard	Paris
Germany	Charité Campus Virchow-Klinikum	Berlin
Germany	Ruhrlandklinik Westdeutsches Lungenzentrum	Essen
Germany	Thoraxklinik am Universitäts Klinikum Heidelberg	Heidelberg
Netherlands	University Medical Center Groningen	Groningen
Sweden	Skane University Hospital	Lund
Sweden	Uppsala University Hospital	Uppsala
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	West of Scotland Regional Heart & Lung Centre - Golden Jubilee National Hospital	Clydebank	West Dunbartonshire Scotland
United Kingdom	The Royal Brompton Hospital & Harefield NHS Foundation Trust	London
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United Kingdom	Sherwood Forest Hospitals NHS	Sutton in Ashfield	Nottinghamshire

Sponsors (1)

Lead Sponsor	Collaborator
Pulmonx, Inc.

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Netherlands,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	PaO2 - Absolute change	Absolute change in PaO2 in the EBV treatment arm at 3 months relative to Baseline.	Between baseline and 3 months
Other	PaO2 - Percent change	Percent change in PaO2 in the EBV treatment arm at 3 months relative to Baseline.	Between baseline and 3 months
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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