Improvement of Cardiovascular Function After Bronchoscopic Lung Volume Reduction Using Endobronchial Valves

NCT04556942 | Unknown DMC

• 1 other identifier: 2019-01682
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

There is increasing evidence showing an association between COPD and cardiovascular disease which is independent from smoking. Recently, it has been shown that FMD of the brachial artery, a surrogate marker of endothelial function, is improving after lung volume reduction surgery (LVRS) in patients with severe emphysema. Thus, hyperinflation might be an independent risk factor of atherosclerosis. Bronchoscopic lung volume reduction (BLVR) using endobronchial valves is a minimal-invasive procedure to decrease hyperinflation in patients with severe emphysema. Eventually, successful BLVR with target atelectasis may have the same effect on FMD compared to LVRS, which would underpin the association between hyperinflation and endothelial function. Patients receiving routinely performed BLVR using endobronchial valves due to severe emphysema with hyperinflation are eligible for this study. After obtaining written informed consent, the participating patients will be randomized into an immediate (within 1-2 weeks) BLVR group and a delayed BLVR group (6-8 weeks). Patients in both groups will undergo baseline measurement of primary and secondary endpoints. Immediate BLVR group will be re-assessed 4-6 weeks after successful EBV treatment, whereas the delayed BLVR group will be re-assessed prior EBV treatment. Results of group 1 and 2 will be compared for final analysis.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Flow Mediated Dilation

Outcome Measures

Primary Outcomes (1)

• Postinterventional change in endothelial function assessed by flow mediated dilation (FMD) (%) before and after the bronchoscopic lung volume reduction (BLVR).

  FMD will be performed by ultrasound using longitudinal images of the brachial artery proximal to the antecubital fossa. Two-dimensional images will be obtained at baseline with Doppler ultrasound imaging to assess arterial diameter and flow velocity. Reactive hyperemia will then be induced by inflation of a pneumatic tourniquet around the forearm to at least 200 mm Hg for 5 minutes. Post-deflation diameter and flow velocity will be monitored continuously from deflation for 210 seconds. To assess endothelial-independent vasodilation maximal brachial artery diameter will be measured continuously for 3 minutes after a single sublingual dose of nitroglycerin (NTG, 0.4 mg). Brachial artery diameter will be measured automatically at the onset of the R wave with dedicated software. Results of endothelial-dependent (FMD) and endothelial-independent (NTG) vasodilation will be expressed as percent change in arterial diameter from the baseline diameter

  FMD measurement will be done at baseline and once again within 6-8 weeks afterwards.

Secondary Outcomes (12)

• Physical activity level (PAL) measuring the steps per day, converting that into a distance in kilometers per day

  Measurement at baseline and once again within 6-8 weeks afterwards.

• Blood pressure (mmHg)

  Measurement at baseline and once again within 6-8 weeks afterwards.

• Heart rate (beats per minute)

  Measurement at baseline and once again within 6-8 weeks afterwards.

• Blood oxygen saturation (%)

  Measurement at baseline and once again within 6-8 weeks afterwards.

• St. George Respiratory Questionnaire (SGRQ)

  Measurement at baseline and once again within 6-8 weeks afterwards.

Study Arms (2)

Group 1 (Immediate Group)

EXPERIMENTAL

Group 1: Will receive at time T0 the baseline study specific measurements of the primary and secondary endpoints: * Flow mediated dilation measurement * Blood pressure, pulse, blood oxygenation saturation measurement * Fit bit tracker counting steps and distance during 7 days * SGRQ (St Georg Respiratory Questionnaire) * Withdrawal of a blood sample for preservation for later examinations This group will receive endobronchial valve placement (EVP) within 1-2 weeks after T0. At T1 which will be 4-6 weeks after EVP the measurements done at T0 will be repeated.

Diagnostic Test: Flow Mediated Dilation (FMD) measurement; Other: Blood pressure, pulse and blood oxygen saturation measurement; Other: ST George Respiratory Questionnaire; Other: Physical activity level (PAL) measurement; Biological: Withdrawal of a blood sample; Procedure: Immediate Bronchoscopic Lung Volume Reduction

Group 2 (Delayed Group)

OTHER

Group 2: Will receive at time T0 the baseline study specific measurements of the primary and secondary endpoints: * Flow mediated dilation measurement * Blood pressure, pulse, blood oxygenation saturation * Fit bit tracker counting steps and distance during 7 days * SGRQ (St Georg Respiratory Questionnaire) * Withdrawal of a blood sample for preservation for later examinations This group will receive endobronchial valve placement (EVP) 6-8 weeks after T0. A few days before that the investigators repeat the measurement taken at T0.

Diagnostic Test: Flow Mediated Dilation (FMD) measurement; Other: Blood pressure, pulse and blood oxygen saturation measurement; Other: ST George Respiratory Questionnaire; Other: Physical activity level (PAL) measurement; Biological: Withdrawal of a blood sample; Procedure: Delayed Bronchoscopic Lung Volume Reduction

Interventions

Flow Mediated Dilation (FMD) measurement DIAGNOSTIC_TEST

FMD measurements will be performed by ultrasound using longitudinal images of the brachial artery using a high-frequency (10.0-MHz) ultrasound scanning probe (VividTM E9 with XDeclearTM; GE Healthcare, Chicago, Illinois, USA) proximal to the antecubital fossa. Two-dimensional images, acquired with electrocardiogram gating, will be obtained at baseline with Doppler ultrasound imaging to assess arterial diameter and flow velocity. Reactive hyperemia will then be induced by inflation of a pneumatic tourniquet around the forearm to at least 200 mm Hg (or \> 50mmHg above systolic pressure) for 5 minutes. Post-deflation diameter and flow velocity will be monitored continuously from deflation for 210 seconds. To assess endothelial-independent vasodilation maximal brachial artery diameter will be measured continuously for 3 minutes after a single sublingual dose of nitroglycerin (NTG, 0.4 mg).

Group 1 (Immediate Group); Group 2 (Delayed Group)

Blood pressure, pulse and blood oxygen saturation measurement OTHER

Blood pressure measurement will be done with a pneumatic tourniquet on the upper arm, after at least 10 minutes rest of the patient. Pulse measurement and oxygen saturation measurement will be done using a finger pulseoximeter, after at least 10 minutes rest of the patient.

Group 1 (Immediate Group); Group 2 (Delayed Group)

ST George Respiratory Questionnaire OTHER

The is a validated and standardized Questionnaire designed to measure health impairment in COPD patients

Group 1 (Immediate Group); Group 2 (Delayed Group)

Physical activity level (PAL) measurement OTHER

PAL will be assessed by the number of steps and kilometers per day using a triaxial accelerometer of a multisensory activity monitor (Fitbit Alta HR; Fitbit Inc., San Francisco, CA, USA). The device is worn like a watch on the wrist. The device is worn always, except while showering or swimming.

Group 1 (Immediate Group); Group 2 (Delayed Group)

Withdrawal of a blood sample BIOLOGICAL

5ml of blood will be withdrawn and preserved after centrifugation at -50 degrees celsius for later analysis at a yet unknown time

Group 1 (Immediate Group); Group 2 (Delayed Group)

Immediate Bronchoscopic Lung Volume Reduction PROCEDURE

Bronchoscopic Lung Volume Reduction by using endobronchial valve placement Within 2 weeks after T0

Group 1 (Immediate Group)

Delayed Bronchoscopic Lung Volume Reduction PROCEDURE

Bronchoscopic Lung Volume Reduction by using endobronchial valve placement Within 6-8 weeks after T0 and 3-4 days after T1

Group 2 (Delayed Group)

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subject between 40 and 75 years of age
• Written informed consent after participant's information signed by patient
• Scheduled for BLVR using endobronchial valves at the University Hospital Zurich
• Dyspnoea at rest or at minimal physical activity (MRC score ≥2), severe limitation of exercise capacity (6-min walk distance \< 500 m).
• COPD (GOLD guidelines) with severe obstructive ventilator defect (FEV1 \<40% predicted)
• Functional aspects of lung emphysema with irreversible hyperinflation, defined as a residual volume to total lung capacity ratio (RV/TLC) of \>0.6
• Pulmonary emphysema confirmed by high resolution computer tomography

You may not qualify if:

• Age \< 40 years, age \> 75 years
• COPD exacerbation within the last 6 weeks or \> 2 exacerbations per year
• Pregnancy
• Lacking ability to form an informed consent (including impaired judgement, communication barriers)
• Current smokers
• Overt active coronary artery disease, left ventricular function impairment
• Pulmonary hypertension with a mean pulmonary artery pressure \>35 mmHg at rest
• Acute bronchopulmonary infection, bronchiectasis on high resolution tomography
• Pulmonary cachexia (body mass index \<18kg/m2)
• Malignant disease with a life expectancy of less than 2 years
• Addiction to alcohol/drugs (= inability to withhold intake during 1 week)

Sponsors & Collaborators

• Daniel Franzen: lead

Study Sites (1)

University Hospital Zurich, Department of Pulmonology

Zurich, 8091, Switzerland

RECRUITING

Related Links

• Projections of global mortality and burden of disease from 2002 to 2030
• Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary
• Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee
• Population-based study of lung function and incidence of heart failure hospitalisations
• The relationship between reduced lung function and cardiovascular mortality: a population-based study and a systematic review of the literature
• Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients
• Hospitalizations and mortality in the Lung Health Study
• Lung Volume Reduction Surgery and Improvement of Endothelial Function and Blood Pressure in Patients with Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial
• Raised CRP levels mark metabolic and functional impairment in advanced COPD
• C-reactive protein and mortality in mild to moderate chronic obstructive pulmonary disease
• Effects of oxygen on autonomic nervous system dysfunction in patients with chronic obstructive pulmonary disease
• Pulmonary and systemic oxidant/antioxidant imbalance in chronic obstructive pulmonary disease
• Arterial Stiffness Is Independently Associated with Emphysema Severity in Patients with Chronic Obstructive Pulmonary Disease
• Determinants of systemic vascular function in patients with stable chronic obstructive pulmonary disease
• Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events
• Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis
• Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study
• Surgical and endoscopic interventions that reduce lung volume for emphysema: a systemic review and meta-analysis
• Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Blood Pressure; Pulse; Weights and Measures

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vital Signs; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Hemodynamics; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Investigative Techniques

Study Officials

• Daniel Franzen, PD Dr. med.

  Universitiy Hospital Zuich, Department of pulmonology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel Franzen, PD Dr. med.

CONTACT

+41 44 255 97 50; daniel.franzen@usz.ch

Jasmin Wani, Pract. med.

CONTACT

+41 44 255 22 21; jasmin.wani@usz.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, PD Dr. med. Daniel Franzen

Model Details: Patients receiving routinely performed bronchoscopic lung volume reduction (BLVR) using endobronchial valves due to severe emphysema with hyperinflation are eligible for this study. After obtaining written informed consent, the participating patients will be randomized into an immediate (within 1-2 weeks) BLVR group and a delayed BLVR group (6-8 weeks) using counted and sealed envelopes. Patients in both groups will undergo baseline study specific measurements of primary and secondary endpoints (T0). The immediate BLVR group will be re-assessed 4-6 weeks after successful endobronchial valve (EBV) treatment, whereas the delayed BLVR group will be re-assessed prior EBV treatment (T1). Results of group 1 and 2 will be compared for final analysis.

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: September 21, 2020
• Study Start: June 5, 2020
• Primary Completion: April 30, 2022
• Study Completion: April 30, 2022
• Last Updated: September 21, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)