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

Phase 3

Recruiting

• Conditions: Altitude Sickness; Right Heart Function; Chronic Obstructive Pulmonary Disease
• Interventions: Drug: Placebo; Drug: Acetazolamide

• Registration Number: NCT04915365
• Lead Sponsor: University of Zurich

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.

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 Timeline

• Study Start: 2021-05-01
• Study First Submitted: 2021-05-31
• Study First Submitted QC: 2021-05-31
• Study First Posted: 2021-06-07
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-01
• Last Update Posted: 2022-11-02
• Primary Completion: 2022-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Acetazolamide	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 tissue dopple S (TDI S) evaluated by echocardiography in the acetazolamide compared to the placebo group

Trial Locations

Locations (1)

National Center of Cardiology and Internal Medicine; 🇰🇬 Bishkek, Kyrgyzstan