Clinical trial NCT04537182: Surgical Compared to Bronchoscopic Lung Volume Reduction in Patients With Severe Emphysema
Official title: Surgical Compared to Bronchoscopic Lung Volume Reduction in Patients With Severe Emphysema: an International Multi-center Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Emphysema
Keywords: LVRS
BLVR
endobronchial valves
heterogeneous empyhsema
non-heterogeneous emphysema
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2020-09-03
Enrollment: 120
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: International, multi-center, open label, morphology- and site-stratified, 1:1 randomized, actively controlled
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* Patients suffering from emphysema (all morphologies, uni- or bilateral distribution) potentially qualifying for both study procedures, LVRS or BLVR (if possible, perfusion scintigraphy within \< 6 month of screening, CT scan within \< 4 months of screening)
* 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:

* 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 ≥ 470m
* 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

Primary outcomes:
measure: Change from baseline value in FEV1 (ml)
timeFrame: 6 months after intervention
Secondary outcomes:
measure: Change from baseline value in FEV1
timeFrame: 3 and 12 months after intervention
measure: Change from baseline value in RV
timeFrame: 3, 6 and 12 months after intervention
measure: Change from baseline value in TLC
timeFrame: 3, 6 and 12 months after intervention
measure: Change from baseline value in RV/TLC
timeFrame: 3, 6 and 12 months after intervention
measure: Change from baseline value in DLCO
timeFrame: 3, 6 and 12 months after intervention
measure: Change from baseline value in 6-minute walking distance
timeFrame: 3, 6 and 12 months after intervention
measure: Change from baseline value in mMRC dyspnea score
timeFrame: 3, 6 and 12 months after intervention
measure: Change from baseline in quality of life (SGRQ, EQ-5D-5L)
timeFrame: 3, 6 and 12 months after intervention
measure: Change from baseline regarding pain (PDI score)
timeFrame: 3, 6 and 12 months after intervention
measure: Change from baseline regarding pain (VAS)
timeFrame: 3, 6 and 12 months after intervention
measure: Incidence of (serious) adverse events / re-interventions
timeFrame: 3, 6 and 12 months after intervention
measure: 30-days mortality
timeFrame: 1 month
measure: 90-days mortality
timeFrame: 3 months
measure: Overall survival rate
timeFrame: 12 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Universitätsklinik für Thoraxchirurgie, Medical University of Vienna
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: Copenhagen
country: Denmark
facility: Rigshospitalet, University of Copenhagen
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
state: Aargau
city: Lausanne
country: Switzerland
facility: Lausanne University Hospital (CHUV)
state: Vaud
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Division of Thoracic Surgery
state: ZH
Study officials:
affiliation: University of Zurich
name: Isabelle Opitz, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: