A Trial on the Effects of Bronchoscopic Lung Volume Reduction in Severe Emphysema. (SOLVE)

A Prospective Randomized Controlled Trial on the Systemic Effects of Bronchoscopic Lung Volume Reduction in Patients With Severe Emphysema.

Rationale: The published clinical trials investigating the bronchoscopic lung volume reduction, showing important patient-related improvements in efficacy, led to the acknowledgement of the treatment in the GOLD-COPD2017 guidelines. Interaction with pulmonary rehabilitation, impact on patient-reported outcomes, physical activity, and extrapulmonary consequences are all topics to gain more insight in. This importantly, to further develop and optimize this innovative and personalized therapy.

Objective: To study in detail the impact and optimal timing of pulmonary rehabilitation (PR) on exercise physiology and patient-reported outcomes and the impact of the bronchoscopic lung volume reduction treatment using endobronchial valves (EBV) on cardiopulmonary function, metabolism and changes in body composition.

Study design: This study is a randomized controlled trial with 3 study-arms. Group 1 will first follow a PR program and afterwards undergo the EBV treatment. Group 2 will first undergo the EBV treatment and approximately 8 weeks later will follow a PR program. Group 3 will only undergo the EBV treatment (and can choose to follow a PR program after completing the 6 month FU visit).

Study population: The study population exist of patients with severe emphysema who undergo a bronchoscopic lung volume reduction treatment using one-way valves.

Intervention: Most patients will undergo a bronchoscopic lung volume reduction treatment using endobronchial valves and a pulmonary rehabilitation program. One group of patient will under a bronchoscopic lung volume reduction treatment using endobronchial valves and can choose whether they also want to follow a pulmonary rehabilitation program afterwards.

Main study parameters: The main study parameter is the difference in change in endurance time measured by an endurance cycle test between the EBV treatment group and the bronchoscopic lung volume reduction + rehabilitation group (EBV+PR).

Study Overview

• Status: Completed
• Conditions: Emphysema
• Intervention / Treatment: Behavioral: Pulmonary rehabilitation; Device: EBV treatment

Detailed Description

Rationale: The published clinical trials investigating the bronchoscopic lung volume reduction, showing important patient-related improvements in efficacy, led to the acknowledgement of the treatment in the GOLD-COPD2017 guidelines. Interaction with pulmonary rehabilitation, impact on patient-reported outcomes, physical activity, and extrapulmonary consequences are all topics to gain more insight in. This importantly, to further develop and optimize this innovative and personalized therapy.

Objective: To study in detail the impact and optimal timing of pulmonary rehabilitation (PR) on exercise physiology and patient-reported outcomes and the impact of the bronchoscopic lung volume reduction treatment using endobronchial valves (EBV) on cardiopulmonary function, metabolism and changes in body composition.

Study design: This study is a randomized controlled trial with 3 study-arms. Group 1 will first follow a PR program and afterwards undergo the EBV treatment. Group 2 will first undergo the EBV treatment and approximately 8 weeks later will follow a PR program. Group 3 will only undergo the EBV treatment (and can choose to follow a PR program after completing the 6 month FU visit).

Study population: The study population exist of patients with severe emphysema who undergo a bronchoscopic lung volume reduction treatment using one-way valves.

Intervention: Most patients will undergo a bronchoscopic lung volume reduction treatment using endobronchial valves and a pulmonary rehabilitation program. One group of patient will under a bronchoscopic lung volume reduction treatment using endobronchial valves and can choose whether they also want to follow a pulmonary rehabilitation program afterwards.

Main study parameters: The main study parameter is the difference in change in endurance time measured by an endurance cycle test between the EBV treatment group and the bronchoscopic lung volume reduction + rehabilitation group (EBV+PR).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This study has no major risks for the participating patients. The patients will be exposed to additional exercise capacity and physical activity measurements, 3 additional questionnaires, a CT scan of the quadriceps muscle, a DEXA scan and peripheral blood collection. Furthermore, a subgroup of patients will be exposed to a cardiac MRI or muscle and fat biopsies. Patient can directly benefit from the EBV treatment and the pulmonary rehabilitation program. Indirect benefit might be achieved, because, at a group level the investigators will learn more about this novel treatment for our severe emphysema patients and will be able to further optimize this treatment.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dirk-Jan Slebos, MD PhD; Phone Number: +31503616161; Email: d.j.slebos@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands
    • University Medical Center Groningen
  • Horn, Netherlands
    • Ciro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• COPD.
• FEV1 ≤45%pred AND FEV1/FVC <70%.
• TLC >100%pred AND RV>175%pred.
• CAT ≥18.
• >50% emphysema destruction @-910HU.
• >95% complete major fissure measured by quantitative CT analysis.
• Non-smoking >6 months.
• Signed informed consent.

Exclusion Criteria:

• PaCO2>8.0 kPa, or PaO2<6.0kPa.
• 6-minute walk test <160m.
• Significant chronic bronchitis, bronchiectasis, or other infectious lung disease.
• 3 of more hospitalizations due to pulmonary infection within last 12 months before baseline assessments
• Previous lobectomy, LVRS, or lung transplantation.
• LVEF<45% and or RVSP>50mmHg.
• Anticoagulant therapy which cannot be weaned off prior to procedure.
• Patient is significantly immunodeficient.
• Involved in other pulmonary drug studies within 30 days prior to this study.
• Pulmonary nodule which requires intervention
• Any disease or condition that interferes with completion of initial or follow-up assessments

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1:PR-EBV treatment; Follow a Pulmonary rehabilitation program PRIOR to the EBV treatment	Behavioral: Pulmonary rehabilitation; Following a PR program; Device: EBV treatment; Bronchoscopic lung volume reduction using endobronchial valves (EBV)
Experimental: Group 2: EBV treatment-PR; Follow a Pulmonary rehabilitation program AFTER the EBV treatment	Behavioral: Pulmonary rehabilitation; Following a PR program; Device: EBV treatment; Bronchoscopic lung volume reduction using endobronchial valves (EBV)
Active Comparator: Group 3: EBV treatment; Only EBV treatment	Device: EBV treatment; Bronchoscopic lung volume reduction using endobronchial valves (EBV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endurance time	The difference in change in endurance time measured by an endurance cycle test between the EBV treatment group and the bronchoscopic lung volume reduction + rehabilitation group (EBV+PR).	After 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary rehabilitation1	• the difference between the EBV treatment group and the EBV+PR group in change in: Physical activity measured by accelerometry	After 6 months
Pulmonary rehabilitation2	• the difference between the EBV treatment group and the EBV+PR group in change in: Lung function measured by bodyplehtysmography	After 6 months
Pulmonary rehabilitation3	• the difference between the EBV treatment group and the EBV+PR group in change in: Exercise capacity measured by an 6-minute walk distance test	After 6 months
Patient reported outcomes	• the change after EBV treatment in fatigue level measured by the CIS questionnaire.	After 6 months
Cardiopulmonary function	• the change after EBV treatment in RVEDVI as measured with cardiac MRI.	After 8 weeks
Metabolism and change in body composition	• the change after EBV treatment in fat-free mass index, fat mass, and fat distribution measured by a dexa scan.	After 8 weeks

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Maastricht University Medical Center; Center of Expertise for Chronic Organ Failure
• Investigators: Principal Investigator: Dirk-Jan Slebos, MD PhD, UMCG

Publications and helpful links

General Publications

• van der Molen MC, Hartman JE, Vanfleteren LEGW, Kerstjens HAM, van Melle JP, Willems TP, Slebos DJ. Reduction of Lung Hyperinflation Improves Cardiac Preload, Contractility, and Output in Emphysema: A Clinical Trial in Patients Who Received Endobronchial Valves. Am J Respir Crit Care Med. 2022 Sep 15;206(6):704-711. doi: 10.1164/rccm.202201-0214OC.

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2018
• Primary Completion (Actual): April 20, 2023
• Study Completion (Actual): April 20, 2023

Study Registration Dates

• First Submitted: March 9, 2018
• First Submitted That Met QC Criteria: March 15, 2018
• First Posted (Actual): March 22, 2018

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• 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: SOLVE

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
• product manufactured in and exported from the U.S.: No