Surgical Compared to Bronchoscopic Lung Volume Reduction in Patients With Severe Emphysema

Study Overview
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Brief Summary
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The investigators plan to perform a randomized controlled trial that compares bilateral lung volume reduction surgery (LVRS) with bronchoscopic lung volume reduction (BLVR) using endobronchial valves in terms of efficacy and patient safety.

Detailed Description
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Advanced lung emphysema has a considerable impact on quality of life in patients with chronic obstructive pulmonary disease. There are positive reports of surgical as well as bronchoscopic volume reduction in selected patients, but data comparing LVRS and BLVR is unfortunately lacking to date. The investigators therefore anticipate that their study will make an important contribution to the worldwide efforts in better understanding selection and management of surgical and bronchoscopic treatment of emphysema patients and that it will be of high public interest.

Official Title
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Surgical Compared to Bronchoscopic Lung Volume Reduction in Patients With Severe Emphysema: an International Multi-center Randomized Controlled Trial

Conditions
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Emphysema

Intervention / Treatment
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* Procedure: Lung volume reduction surgery
* Procedure: Bronchoscopic lung volume reduction with valves


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients suffering from emphysema (all morphologies) potentially qualifying for both study procedures, LVRS or BLVR (perfusion scintigraphy within < 6 month of screening, CT scan within < 3 months of screening) • Patients with bilateral emphysema not exceeding perfusion and/or volume side differences of 70%:30% and therefore allowing a primary bilateral LVRS (borderline perfusion results regarding side dominance (+/- 5%) are accepted as long as CT morphology and volume-based perfusion morphology are suitable for bilateral LVRS) Age ≥ 30 and ≤ 80 years Body Mass Index (BMI) ≥ 16, but ≤ 35 kg/m2 Non-smoking for 3 months prior to screening interview Patient is able to understand and willing to sign a written informed consent document Exclusion Criteria: Post-bronchodilator FEV1 more than 50% predicted TLC less than 100 % predicted, RV less than 175% predicted, RV/TLC less than 58% predicted, and DLCO ≤ 20% predicted in homogeneous emphysema and DLCO ≤ 15% in heterogeneous emphysema, respectively PaO2 ≤ 6.0 kPa (45mm Hg) at ambient air (only applicable for homogeneous morphology!) PaCO2 ≥ 6.6 kPa (50 mmHg) at ambient air (only applicable for homogeneous morphology!) Patients with incomplete interlobar fissures as revealed by quantitative computed tomography analysis with StratX® (fissure completeness ≤ 80%) Patients with collateral ventilation as evidenced by bronchoscopic Chartis® measurement (only performed if fissure completeness according to StratX® is <95%) 6-minute walking distance ≥ 450m More than two COPD exacerbation episodes requiring hospitalization in the last year More than two instances of pneumonia episodes in the last year Unplanned weight loss ≥ 10% within 90 days prior to enrollment Pulmonary hypertension as evidenced by Delta Psyst RV-RA > 35 mmHg on recent echocardiography (within 3 months prior to screening) and confirmed by RHC (mPAP ≥ 35 mmHg) and signs of moderate to severe RV dysfunction. Evidence of left ventricular ejection fraction (LVEF) less than 45% on recent echocardiography (within 3 months prior to screening) History of exercise-related syncope Myocardial infarction or congestive heart failure within 6 months of screening Clinically significant arrhythmias that might put the patient at risk in regard to the interventions Prior LVR (any method), bullectomy, or lobectomy Clinically significant bronchiectasis with expectoration of ≥ 2 tablespoons/day. Pulmonary nodule requiring surgery Unable to safely discontinue anticoagulants or dual antiplatelet therapy for 7 days Patients with a life expectancy of less than one year Any disease or condition that interferes with completion of initial or follow-up assessment Currently listed for lung transplantation Daily dose of prednisone ≥ 10mg Current enrollment in another clinical trial studying an experimental treatment.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: International, multi-center, open label, morphology- and site-stratified, 1:1 randomized, actively controlled
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LVRS treatment group<br>A bilateral lung volume reduction surgery (LVRS) by video-assisted thoracoscopic surgery (VATS) is performed under general anesthesia with double lumen endobronchial intubation. Unilateral treatment is accepted in cases with severe adhesions or intraoperative instability making a bilateral procedure unsafe. | Procedure: Lung volume reduction surgery<br>* Lung volume reduction by surgery<br>* Other names: LVRS;|
| Active Comparator: BLVR study group<br>Unilateral bronchoscopic lung volume reduction with endobronchial valves (EBV) is performed using a flexible bronchoscope under general anesthesia and under full attendance of an anesthesiologist. Valves are placed unilaterally in segmental or subsegmental bronchi in the target lobe with the goal of complete atelectasis. | Procedure: Bronchoscopic lung volume reduction with valves<br>* Lung volume reduction with endobronchial valves.<br>* Other names: BLVR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline value in FEV1 (ml) | Percent change in FEV1 | 6 months after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline value in FEV1 | Percent change in forced expiratory volume (FEV1) | 3 and 12 months after intervention | 
| Change from baseline value in RV | Percent change in residual volume (RV) | 3, 6 and 12 months after intervention | 
| Change from baseline value in TLC | Percent change in total lung capacity (TLC) | 3, 6 and 12 months after intervention | 
| Change from baseline value in RV/TLC | Percent change in RV-to-TLC ratio | 3, 6 and 12 months after intervention | 
| Change from baseline value in DLCO | Percent change in diffusion capacity (DLCO) | 3, 6 and 12 months after intervention | 
| Change from baseline value in 6-minute walking distance | Distance that can be walked within 6 minutes | 3, 6 and 12 months after intervention | 
| Change from baseline value in mMRC dyspnea score | Degree of disability that breathlessness poses on day-to-day activities on a scale from 0 to 4 | 3, 6 and 12 months after intervention | 
| Change from baseline in quality of life (SGRQ, EQ-5D-5L) | St. George's Respiratory Questionnaire to assess quality of life | 3, 6 and 12 months after intervention | 
| Change from baseline regarding pain (PDI score) | Pain Disability Index score | 3, 6 and 12 months after intervention | 
| Change from baseline regarding pain (VAS) | Pain assessment with visual analog scale (VAS) | 3, 6 and 12 months after intervention | 
| Incidence of (serious) adverse events / re-interventions | Number and degree of adverse events after intervention | 3, 6 and 12 months after intervention | 
| 30-days mortality | Number of deaths (all causes) 1 month after intervention | 1 month | 
| 90-days mortality | Number of deaths (all causes) 3 months after intervention | 3 months | 
| Overall survival rate | Percentage of patients alive 1 year after intervention | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LVRS, BLVR, endobronchial valves, heterogeneous empyhsema, non-heterogeneous emphysema