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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Emphysema
• Intervention / Treatment: Procedure: Lung volume reduction surgery; Procedure: Bronchoscopic lung volume reduction with valves

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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Isabelle Opitz, Prof. MD; Phone Number: +41 44 255 11 11; Email: isabelle.schmitt-opitz@usz.ch
• Study Contact Backup: Name: Nadine Bosbach, MSc; Phone Number: +41 44 255 92 30; Email: nadine.bosbach@usz.ch

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • University Hospital Leuven
    • Contact: Laurens Ceulemans, Prof MD; Email: laurens.ceulemans@uzleuven.be
• Switzerland
  • Aargau
    • Aarau, Aargau, Switzerland, 5001
      • Recruiting
      • Kantonsspital Aarau
      • Contact: Franco Gambazzi, PD MD; Email: franco.gambazzi@ksa.ch
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Recruiting
      • Lausanne University Hospital (CHUV)
      • Contact: Thorsten Krueger, Prof MD; Email: thorsten.krueger@chuv.ch
  • ZH
    • Zurich, ZH, Switzerland, 8091
      • Recruiting
      • University Hospital Zurich, Division of Thoracic Surgery
      • Contact: Isabelle Opitz, Prof MD; Phone Number: +41 44 255 11 11; Email: isabelle.schmitt-opitz@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LVRS treatment group; 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; Lung volume reduction by surgery; Other Names: LVRS
Active Comparator: BLVR study group; 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; Lung volume reduction with endobronchial valves.; Other Names: BLVR

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Isabelle Opitz, Professor, MD
• Investigators: Principal Investigator: Isabelle Opitz, Prof. MD, University of Zurich

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: August 20, 2020
• First Submitted That Met QC Criteria: August 28, 2020
• First Posted (Actual): September 3, 2020

Study Record Updates

• Last Update Posted (Actual): May 27, 2022
• Last Update Submitted That Met QC Criteria: May 23, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: LVRS; BLVR; endobronchial valves; heterogeneous empyhsema; non-heterogeneous emphysema
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Emphysema
• Other Study ID Numbers: SINCERE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No