Effect of Acetazolamide on Right Heart Function at Rest in Lowlanders With COPD Traveling to High Altitude

Sponsor

University of Zurich (Other)

Overall Status

Recruiting

CT.gov ID

NCT04915365

Collaborator

National Center of Cardiology and Internal Medicine, Kyrgyz Republic (Other)

100

Enrollment

Location

Arms

Anticipated Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this randomized, placebo-controlled double-blind trial is to evaluate the effect of acetazolamide on right heart function at rest in lowlanders with chronic obstructive pulmonary disease (COPD) traveling to high altitude (HA) and developing early signs of altitude-illness.

Condition or Disease	Intervention/Treatment	Phase
Right Heart Function Chronic Obstructive Pulmonary Disease Altitude Sickness	Drug: Acetazolamide Drug: Placebo	Phase 3

Detailed Description

This randomized placebo-controlled, double-blind, parallel-design trial will evaluate effect of acetazolamide on right heart function in lowlanders with chronic obstructive pulmonary disease (COPD) travelling to high altitude and developping early symptoms and/or signs of impending altitude-illness. Qualifying participants will be randomized 1:1 to acetazolamide or placebo treatment during their further stay of 2 days at 3'100 m.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

randomized, placebo-controlled, double-blindrandomized, placebo-controlled, double-blind

Masking:

None (Open Label)

Masking Description:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) An independent pharmacist will prepare identically looking active and placebo capsules labelled with secret codes. Codes will be concealed to investigators and patients until completion of data analysis.

Primary Purpose:

Prevention

Official Title:

Effect of Acetazolamide on Right Heart Function at Rest in Lowlanders With Chronic Obstructive Pulmunary Disease (COPD) Traveling to High Altitude

Anticipated Study Start Date :

Jun 1, 2021

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Acetazolamide Acetazolamide (oral capsules @125 mg), starting dose 3 capsules (375 mg), subsequent doses 1 capsule (125 mg) in the morning, 2 capsules (250 mg) in the evening, administered in qualifying participants, during the stay at 3100 m.	Drug: Acetazolamide Acetazolamide (oral capsules @125 mg), starting dose 3 capsules (375 mg), subsequent doses 1 capsule (125 mg) in the morning, 2 capsules (250 mg) in the evening, administered in qualifying participants, during the stay at 3100 m. Other Names: Acetazolamide, oral capsule
Placebo Comparator: Placebo Placebo (oral capsules, identically looking as active drug), starting dose 3 capsules, subsequent doses 1 capsule in the morning, 2 capsules in the evening, administered in qualifying participants, during the stay at 3100 m.	Drug: Placebo Placebo (oral capsules, identically looking as active drug), starting dose 3 capsules, subsequent doses 1 capsule in the morning, 2 capsules in the evening, administered in qualifying participants, during the stay at 3100 m. Other Names: Placebo, oral capsule

Arm

Intervention/Treatment

Experimental: Acetazolamide

Acetazolamide (oral capsules @125 mg), starting dose 3 capsules (375 mg), subsequent doses 1 capsule (125 mg) in the morning, 2 capsules (250 mg) in the evening, administered in qualifying participants, during the stay at 3100 m.

Drug: Acetazolamide

Other Names:

Acetazolamide, oral capsule

Placebo Comparator: Placebo

Placebo (oral capsules, identically looking as active drug), starting dose 3 capsules, subsequent doses 1 capsule in the morning, 2 capsules in the evening, administered in qualifying participants, during the stay at 3100 m.

Drug: Placebo

Other Names:

Placebo, oral capsule

Outcome Measures

Primary Outcome Measures

Difference in change of pulmonary artery pressure [3 days]
Difference in change of pulmonary artery pressure (RV/RA) evaluated by echocardiography at 3100 m in the acetazolamide compared to the placebo group

Secondary Outcome Measures

Difference in change of pulmonary artery pressure (RV/RA) low altitude versus high altitude [3 days]
Difference in change of pulmonary artery pressure evaluated by echocardiography from 760 m baseline measurement to measurement at 3100 m in the acetazolamide compared to the placebo group
Difference in cardiac output [3 days]
Difference in change of cardiac output evaluated by echocardiography in the acetazolamide compared to the placebo group
Difference in right heart dimensions [3 days]
Difference in change of right heart dimensions evaluated by echocardiography in the acetazolamide compared to the placebo group
Difference in right heart function [3 days]
Difference in change of tricuspid annular plane systolic sxcursion (TAPSE) evaluated by echocardiography in the acetazolamide compared to the placebo group
Difference in right heart function [3 days]
Difference in change of fraction area change (FAC) evaluated by echocardiography in the acetazolamide compared to the placebo group
Difference in right heart function [3 days]
Difference in change of tissue dopple S (TDI S) evaluated by echocardiography in the acetazolamide compared to the placebo group

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women, age 35-75 y, living at low altitude (<800 m).
COPD diagnosed according to the Global Initiative for Obstructive Lung Disease (GOLD) guidelines, FEV1 40-80% predicted, pulse oximetry

≥92%, PaCO2 <6 kPa, breathing ambient air at 760 m.

One of the following early signs and/or symptoms of impending altitudeillness identified by self-monitoring during ascent to or stay at 3100 m:
Pulse oximetry SpO2≤84%
Headache or nausea/vomiting or fatigue/weakness or dizziness/lightheadedness of at least moderate intensity

Exclusion Criteria:

COPD exacerbation, very severe COPD with hypoxemia or hypercapnia at 760 m (see above).
Other lung disease, relevant comorbidities (such as uncontrolled cardiovascular disease, i.e., unstable arterial hypertension, coronary artery disease; previous stroke; obesity (body mass index >35 kg/m2); internal, neurologic, rheumatologic or psychiatric disease; current heavy smoking (>20 cigarettes per day).
Renal failure and/or allergy to sulfonamides.
Patients who do not have early signs and/or signs of impending altitudeillness by self-monitoring (as defined above) at 3'100m will not be included.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Center of Cardiology and Internal Medicine	Bishkek		Kyrgyzstan	720040

Sponsors and Collaborators

University of Zurich
National Center of Cardiology and Internal Medicine, Kyrgyz Republic

Investigators

Study Chair: Silvia Ulrich, Prof, University Hospital, Zürich, Switzerland
Study Director: Talant M Sooronbaev, MD, National Center of Cardiology and Internal Medicine, Bishkek, Kyrgyzstan