Effect of Acetazolamide on Right Ventricular Function During Exercise in Patients With Respiratory Disease at Altitude

Study Overview
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Brief Summary
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This trial will evaluate the effect of acetazolamide (375 mg per day) vs. placebo on right ventricular function during exercise at acute altitude exposure in patients with COPD.

Detailed Description
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This is a randomized, placebo-controlled, double-blind parallel trial evaluating the effect of acetazolamide (375 mg per day) vs. placebo on right ventricular function during exercise in lowlanders with chronic obstructive pulmonary disease travelling to altitude. Participants living in the Bishkek area, Kyrgyzstan (760m), will be transferred by car within 4h to the Tuja Ashu high altitude clinic (3200 m), and stay there for 2 days. Acetazolamide 375mg/day (or placebo) will be administered 24 hours before departure at 760 m and during the stay at altitude. Outcomes will be assessed during the stay at 3200 m. Right ventricular function will be assessed during graded cycling on an ergometer by transthoracic echocardiography.

Official Title
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Effect of Acetazolamide on Right Ventricular Function During Exercise in Patients With Chronic Obstructive Pulmonary Disease at Altitude. A Randomized, Placebo-controlled, Double-blind Parallel Trial.

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: ACETAZOLAMIDE oral capsule
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients, age 18-75 yrs. COPD diagnosed according to GOLD, FEV1 40-80% predicted, SpO2 ≥92% at 750 m. Born, raised and currently living at low altitude (<800m). Written informed consent. Exclusion Criteria: COPD exacerbation, very severe COPD with hypoxemia at low altitude (FEV1/FVC <0.7, FEV1 <40% predicted, oxygen saturation on room air <92% at 750 m). Comorbidities such as uncontrolled cardiovascular disease, i.e., unstable systemic arterial hypertension, coronary artery disease; previous stroke; OSA; pneumothorax in the last 2 months. Internal, neurologic, rheumatologic or psychiatric disease including current heavy smoking (>20 cigarettes per day) Known renal failure or allergy to acetazolamide and other sulfonamides

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ACETAZOLAMIDE oral capsule<br>Acetazolamide 375mg/day (capsule @125 mg: 1 in the morning, 2 in the evening), orally. Medication starts 24 hours before ascent to 3200m until the morning after the second night at 3200m | Drug: ACETAZOLAMIDE oral capsule<br>* Administration of 125mg acetazolamide in the morning, 250mg in the evening, starting 24 hours before departure to 3200m<br>|
| Placebo Comparator: PLACEBO oral capsule<br>Placebo (capsules identically looking as acetazolamide capsules: 1 in the morning, 2 in the evening), orally. Medication starts 24 hours before ascent to 3200m until the morning after the second night at 3200m. | Drug: Placebo oral capsule<br>* Administration of equally looking placebo capsules in the morning and evening, starting 24 hours before departure to 3200m<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pulmonary artery pressure during exercise | Difference in change of tricuspid pressure gradient during exercise between acetazolamide and placebo group at altitude, measured by transthoracic echocardiography during graded cycling on an ergometer | Day 2 at 3200m | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pulmonary artery pressure during exercise | Difference in altitude-induced change of tricuspid pressure gradient during exercise between acetazolamide and placebo group, measured by transthoracic echocardiography during graded cycling on an ergometer | Day 2 at 760 m and 3200 m | 
| cardiac output during exercise | Difference in change of cardiac output during exercise between acetazolamide and placebo group at altitude, measured by transthoracic echocardiography during graded cycling on an ergometer | Day 2 at 3200m | 
| cardiac output during exercise | Difference in altitude-induced change of cardiac output during exercise between acetazolamide and placebo group, measured by transthoracic echocardiography during graded cycling on an ergometer | Day 2 at 760 m and 3200 m | 
| PAP/CO slope during exercise | Difference in change of PAP/CO slope during exercise between acetazolamide and placebo group at altitude, measured by transthoracic echocardiography during graded cycling on an ergometer | Day 2 at 3200m | 
| PAP/CO slope during exercise | Difference in altitude-induced change of PAP/CO slope during exercise between acetazolamide and placebo group, measured by transthoracic echocardiography during graded cycling on an ergometer | Day 2 at 760 m and 3200 m | 
| Oxygen saturation | Difference in altitude-induced change during exercise of oxygen saturation between acetazolamide and placebo group, measured by pulse oximeter | Day 2 and 3200 m | 
| Oxygen saturation | Difference in change of oxygen saturation during exercise between acetazolamide and placebo group, measured by pulse oximeter | Day 2 at 760 m and 3200 m | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, echocardiography, right ventricular function, obstructive airway disease, emphysema, acetazolamide, altitude