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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04556942
Recruitment Status : Recruiting
First Posted : September 21, 2020
Last Update Posted : September 21, 2020
Sponsor:
Information provided by (Responsible Party):
Daniel Franzen, University of Zurich

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.


Condition or disease Intervention/treatment Phase
Pulmonary Disease, Chronic Obstructive 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 Procedure: Delayed Bronchoscopic Lung Volume Reduction Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Improvement of Cardiovascular Function After Bronchoscopic Lung Volume Reduction Using Endobronchial Valves in Patients With Severe Emphysema: A Randomized Controlled Trial
Actual Study Start Date : June 5, 2020
Estimated Primary Completion Date : April 30, 2022
Estimated Study Completion Date : April 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Emphysema

Arm Intervention/treatment
Experimental: Group 1 (Immediate Group)

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
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).

Other: Blood pressure, pulse and blood oxygen saturation measurement

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.


Other: ST George Respiratory Questionnaire
The is a validated and standardized Questionnaire designed to measure health impairment in COPD patients

Other: Physical activity level (PAL) measurement
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.

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5ml of blood will be withdrawn and preserved after centrifugation at -50 degrees celsius for later analysis at a yet unknown time

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

Group 2 (Delayed Group)

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
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).

Other: Blood pressure, pulse and blood oxygen saturation measurement

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.


Other: ST George Respiratory Questionnaire
The is a validated and standardized Questionnaire designed to measure health impairment in COPD patients

Other: Physical activity level (PAL) measurement
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.

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

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




Primary Outcome Measures :
  1. Postinterventional change in endothelial function assessed by flow mediated dilation (FMD) (%) before and after the bronchoscopic lung volume reduction (BLVR). [ Time Frame: FMD measurement will be done at baseline and once again within 6-8 weeks afterwards. ]
    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


Secondary Outcome Measures :
  1. Physical activity level (PAL) measuring the steps per day, converting that into a distance in kilometers per day [ Time Frame: Measurement at baseline and once again within 6-8 weeks afterwards. ]

    PAL will be assessed by the measurement of the number of steps per day. The device will calculate from the number of steps per day the distance in kilometers per day knowing the height of the patient. The height will be programmed into the device beforehand.

    To measure the steps per day the investigator uses 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 of the patient. The device is worn always, except while showering or swimming. At both visits patients will receive the device and wear it for seven days for data collection and send it back via postal mail afterwards.


  2. Blood pressure (mmHg) [ Time Frame: Measurement at baseline and once again within 6-8 weeks afterwards. ]
    Measurement of the systolic and diastolic blood pressure is done after 10 minutes of rest using a pneumatic tourniquet and a pulseoximeter.

  3. Heart rate (beats per minute) [ Time Frame: Measurement at baseline and once again within 6-8 weeks afterwards. ]
    Measurement is done after 10 minutes of rest using a pulseoximeter.

  4. Blood oxygen saturation (%) [ Time Frame: Measurement at baseline and once again within 6-8 weeks afterwards. ]
    Measurement is done after 10 minutes of rest using a pulseoximeter.

  5. St. George Respiratory Questionnaire (SGRQ) [ Time Frame: Measurement at baseline and once again within 6-8 weeks afterwards. ]

    Standardized questionaire to assess the health impaired through COPD. It is in two parts. Part I produces the Symptoms score, and Part 2 the Activity and Impacts scores. A Total score is also produced. An excel-based scoring calculator is used to analyze the collected data. All positive responses are entered as 1 and all negative responses are entered as 0.

    Three component scores are calculated for the SGRQ:

    • Symptoms: this component is concerned with the effect of respiratory symptoms, their frequency and severity.
    • Activity: concerned with activities that cause or are limited by breathlessness
    • Impacts: covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease A Total score is also calculated which summarises the impact of the disease on overall health status. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status.

  6. 6-minute walking distance (6-MWD) in meters [ Time Frame: Done during the routine visit before BLVR, which is before the study phase and it will be repeated during the routine follow-up 4-6 weeks after BLVR ]
    This assessment is not study specific. It is done during the regular assessment before BLVR and repeated after BLVR. It measures the distance a patient can go within 6 minutes.

  7. Forced Expiratory Volume in first second (FEV1) in liters [ Time Frame: Done during the routine visit before BLVR, which is before the study phase and it will be repeated during the routine follow-up 4-6 weeks after BLVR ]
    This assessment is not study specific. It is done during the regular assessment before BLVR and repeated after BLVR. It measures the volume in liters that is exhaled during the first second of forced exhalation during a pulmonary function test.

  8. Residual Volume (RV) in liters [ Time Frame: Done during the routine visit before BLVR, which is before the study phase and it will be repeated during the routine follow-up 4-6 weeks after BLVR ]
    This assessment is not study specific. It is done during the regular assessment before BLVR and repeated after BLVR. During a pulmonary function test it measures the volume in liters that remains in the lungs after maximal exhalation .

  9. Residual Volume (RV)/ Total Lung Capacity (TLC) in percentage [ Time Frame: Done during the routine visit before BLVR, which is before the study phase and it will be repeated during the routine follow-up 4-6 weeks after BLVR ]
    This assessment is not study specific. It is done during the regular assessment before BLVR and repeated after BLVR. During a pulmonary function test it measures the Residual Volume to Total Lung Capacity Ratio expressed as percentage.

  10. CO-Diffusion Capacity (DLCO) in percentage [ Time Frame: Done during the routine visit before BLVR, which is before the study phase and it will be repeated during the routine follow-up 4-6 weeks after BLVR ]
    This assessment is not study specific. It is done during the regular assessment before BLVR and repeated after BLVR. It measures the transfer of gas from air in the lung, to the red blood cells in lung blood vessels. It is part of a comprehensive series of pulmonary function tests to determine the overall ability of the lung to transport gas into and out of the blood.

  11. Number of participants with relevant change in C-reactive protein before and after BLVR [ Time Frame: Done during the routine visit before BLVR, which is before the study phase and it will be repeated during the routine follow-up 4-6 weeks after BLVR ]
    This assessment is not study specific. In the blood C-reactive protein will be measured. It is done during the regular assessment before BLVR and repeated after BLVR. The investigator will observe if the value changes before and after the intervention.

  12. Number of participants with relevant change NT-proBNP before and after BLVR [ Time Frame: Done during the routine visit before BLVR, which before is the study phase and it will be repeated during the routine follow-up 4-6 weeks after BLVR ]
    This assessment is not study specific. In the blood NT-pro-BNP will be measured. It is done during the regular assessment before BLVR and repeated after BLVR. The investigator will observe if the value changes before and after the intervention.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04556942


Contacts
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Contact: Daniel Franzen, PD Dr. med. +41 44 255 97 50 daniel.franzen@usz.ch
Contact: Jasmin Wani, Pract. med. +41 44 255 22 21 jasmin.wani@usz.ch

Locations
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Switzerland
University Hospital Zurich, Department of Pulmonology Recruiting
Zurich, Switzerland, 8091
Contact: Daniel Franzen, PD Dr. med.    +41 44 255 97 50    daniel.franzen@usz.ch   
Contact: Jasmin Wani, Pract. med.    +41442552221    jasmin.wani@usz.ch   
Sub-Investigator: Jasmin Wani, Pract. med.         
Sponsors and Collaborators
Daniel Franzen
Investigators
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Principal Investigator: Daniel Franzen, PD Dr. med. Universitiy Hospital Zuich, Department of pulmonology
Additional Information:

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Responsible Party: Daniel Franzen, Principal Investigator, PD Dr. med. Daniel Franzen, University of Zurich
ClinicalTrials.gov Identifier: NCT04556942    
Other Study ID Numbers: 2019-01682
First Posted: September 21, 2020    Key Record Dates
Last Update Posted: September 21, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daniel Franzen, University of Zurich:
Flow Mediated Dilation
Additional relevant MeSH terms:
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Pulmonary Disease, Chronic Obstructive
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive