LVRS Versus BLVR in Patients With Homogenous Emphysema, CLUB-HE Trial

Study Overview
=================
Brief Summary
-----------------
This is a prospective randomized clinical trial comparing surgical and bronchoscopic lung volume reduction in patients with advanced homogeneous emphysema suitable for both procedures.

Detailed Description
-----------------
Lung volume reduction surgery (LVRS) as well as bronchoscopic lung volume reduction (BLVR) provide functional improvements in selected patients with homogenous emphysema and pronounced hyperinflation. A direct comparison of LVRS and BLVR in patients with homogenous emphysema is not available, thus the study will provide important data to guide treatment selection in this patient population.

Official Title
-----------------
Comparison of Lung Volume Reduction Surgery Versus Bronchoscopic Lung Volume Reduction in Patients With Homogenous Emphysema: A Prospective Randomized Trial

Conditions
-----------------
Emphysema or COPD

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: COPD III-IV Age ≥ 18 years FEV1 < 50% predicted after bronchodilatation Significant hyperinflation (TLC >100% predicted, RV > 200% predicted, RV/TLC > 60%) Non-smoker or ex-smoker for > 3 months (documented by cotinine testing) 6 MWT >150 m and ≤ 450m MRC dyspnea score > 3 Homogenous emphysema as assessed by HR-CT (< 15% difference in emphysema destruction score between target lobe and ipsilateral lobe) [16, 17] Uni- or bilateral collateral ventilation (CV) negative result assessed fissure completeness>95% in QCT and confirmed by a bronchoscopic procedure (Chartis©) Optimal medical therapy for > 3months, sufficient rehabilitation status with no need for further training/rehabilitation or rehabilitation within 6 months prior to intervention. Body Mass Index (BMI) > 18, but < 35 kg/m2 Daily dose of prednisone ≤ 10mg Exclusion Criteria: Contraindication against either LVRS or BLVR and/or to surgery and bronchoscopy in general Major comorbidities limiting survival Age ≥ 80 years Nicotine abuse within 3 months (documented by cotinine testing) Predominance of either left or right lung of >70% in perfusion SPECT scintigraphy FEV1 and/or DLCO <20% predicted (post bronchodilatation) Untreated Hypoxemia (PaO2 < 50 mmHg) Untreated Hypercapnia (PaCO2 > 50 mmHg) Significant pulmonary fibrosis or bronchiectasis Destroyed/vanished lung on HR-CT Previous chest surgery or bronchoscopic interventions Pulmonary hypertension (sPAP > 35 mmHg) Active waiting list for lung transplantation Patient is not able to understand and willing to sign a written informed consent document. Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: single center, 1:1 randomized, open label, controlled
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lung volume reduction surgery arm<br>Bilateral videothoracoscopic lung volume reduction surgery by wedge resection. Unilateral procedures are possible in case of severe adhesions or intraoperative instability. In these cases a staged approach with contralateral LVRS within 3 months is possible. | Procedure: Lung volume reduction surgery<br>* Surgical lung volume reduction<br>|
| Active Comparator: Bronchoscopic lung volume reduction arm<br>Primarily unilateral bronchoscopic lung volume reduction by endobronchial valves. If a bilateral procedure is feasible it must be performed within 3 months after the first intervention. | Procedure: Bronchoscopic lung volume reduction<br>* Bronchoscopic lung volume reduction by endobronchial valves<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FEV1 compared to baseline (deltaFEV1) | Percent change in FEV1 | 6 months post intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BODE Index (Body mass index, airflow obstruction, dyspnoea and exercise capacity in chronic obstructive pulmonary disease) | Combined score including BMI, FEV1, 6 MWT, MRC dyspnoea score; range 0 (best) - 10 (worst) | 3, 6 months post intervention | 
| Change in TLC | Percent change in Total Lung Capacity | 3, 6 months post intervention | 
| Change in RV | Percent change in Residual Volume | 3, 6 months post intervention | 
| Change in RV/TLC | Percent change in RV/TLC ratio | 3, 6 months post intervention | 
| Change in DLCO | Percent change in diffusion capacity | 3, 6 months post intervention | 
| Change in systolic pulmonary artery pressure | measured by echocardiography | 6 months post intervention | 
| Changes in health-related quality of life measured by SGRQ | St. George´s Respiratory Questionnaire (score 0-100, higher scores indicating more limitations) | 3, 6 months post intervention | 
| Changes in respiratory health status measured by CAT | COPD Assessment Test (CAT) | 3, 6 months post intervention | 
| Mortality | Number of deaths 30 days post intervention | 30 days post intervention | 
| Overall survival | Percent of patients alive 6 months post intervention | 6 months post intervention | 
| Incidence of (serious) adverse events | Number of events periprocedural, 1, 3 and 6 months post intervention | Periprocedural, 1, 3, 6 months post intervention |