COPD, Heterogeneous Emphysema
Conditions
Keywords
Endoscopic lung volume reduction, Endobronchial valves
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.
Interventions
DEVICEELVR (Endoscopic Lung Volume Reduction) with Zephyr Valves
Sponsors
Pulmonx Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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) - 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). |
| 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. |
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| PaO2 - Percent change | Between baseline and 3 months | Percent change in PaO2 in the EBV treatment arm at 3 months relative to Baseline. |
| Residual Volume (RV) - Absolute change | Between Baseline and 3, 6 and 12, 18 and 24 months | 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. |
| Residual Volume (RV) - Percent change | Between Baseline and 3, 6 and 12, 18 and 24 months | 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. |
| EQ-5D Summary Index - Absolute change | Between Baseline and 3, 6, 12, 18 and 24 months | 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. |
| EQ-5D Summary Index Percent change | Between Baseline and 3, 6, 12, 18 and 24 months | 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. |
| Mean number of additional hospitalizations and/or visits caused by respiratory conditions | Between baseline and 24 months | 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. |
| PaO2 - Absolute change | Between baseline and 3 months | Absolute change in PaO2 in the EBV treatment arm at 3 months relative to Baseline. |
| Adverse Events | Between baseline and 24 months | 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). |
Countries
Belgium, France, Germany, Netherlands, Sweden, United Kingdom
Outcome results
None listed