Clinical trial NCT03474471: A Trial on the Effects of Bronchoscopic Lung Volume Reduction in Severe Emphysema.
Official title: A Prospective Randomized Controlled Trial on the Systemic Effects of Bronchoscopic Lung Volume Reduction in Patients With Severe Emphysema.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Emphysema
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Maastricht University Medical Center
name: Center of Expertise for Chronic Organ Failure
First posted: 2018-03-22
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Endurance time
timeFrame: After 6 months
Secondary outcomes:
measure: Pulmonary rehabilitation1
timeFrame: After 6 months
measure: Pulmonary rehabilitation2
timeFrame: After 6 months
measure: Pulmonary rehabilitation3
timeFrame: After 6 months
measure: Patient reported outcomes
timeFrame: After 6 months
measure: Cardiopulmonary function
timeFrame: After 8 weeks
measure: Metabolism and change in body composition
timeFrame: After 8 weeks
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Horn
country: Netherlands
facility: CIRO
Study officials:
affiliation: UMCG
name: Dirk-Jan Slebos, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.