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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Right Heart Function, Chronic Obstructive Pulmonary Disease, Altitude Sickness

Intervention / Treatment
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* Drug: Acetazolamide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, placebo-controlled, double-blind
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetazolamide<br>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<br>* 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.<br>* Other names: Acetazolamide, oral capsule;|
| Placebo Comparator: Placebo<br>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<br>* 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.<br>* Other names: Placebo, oral capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in change of pulmonary artery pressure | Difference in change of pulmonary artery pressure (RV/RA) evaluated by echocardiography at 3100 m in the acetazolamide compared to the placebo group | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in change of pulmonary artery pressure (RV/RA) low altitude versus high altitude | 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 | 3 days | 
| Difference in cardiac output | Difference in change of cardiac output evaluated by echocardiography in the acetazolamide compared to the placebo group | 3 days | 
| Difference in right heart dimensions | Difference in change of right heart dimensions evaluated by echocardiography in the acetazolamide compared to the placebo group | 3 days | 
| Difference in right heart function | Difference in change of tricuspid annular plane systolic sxcursion (TAPSE) evaluated by echocardiography in the acetazolamide compared to the placebo group | 3 days | 
| Difference in right heart function | Difference in change of fraction area change (FAC) evaluated by echocardiography in the acetazolamide compared to the placebo group | 3 days | 
| Difference in right heart function | Difference in change of tissue dopple S (TDI S) evaluated by echocardiography in the acetazolamide compared to the placebo group | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acetazolamide, Mountain sickness, Pulmonary Hypertension