Effect of Acetazolamide on Right Ventricular Function at Rest 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 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 at rest 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 by transthoracic echocardiography.

Official Title
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Effect of Acetazolamide on Right Ventricular Function at Rest 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 | Difference in altitude-induced change of pulmonary artery pressure (PAP) between acetazolamide and placebo group, measured by transthoracic echocardiography (tricuspid pressure gradient and pulmonary valve acceleration time) | Day 2 at 760m and 3200m | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pulmonary artery pressure | Difference at altitude of pulmonary artery pressure (PAP) between acetazolamide and placebo group, measured by transthoracic echocardiography (tricuspid pressure gradient and pulmonary valve acceleration time) | Day 2 at 3200m | 
| cardiac output | Difference in altitude-induced change of cardiac output between acetazolamide and placebo group, measured by transthoracic echocardiography | Day 2 at 760m and 3200m | 
| cardiac output | Difference at altitude between acetazolamide and placebo group in cardiac output, measured by transthoracic echocardiography | Day 2 at 3200m | 
| right heart dimensions | Difference in altitude-induced change of right heart dimensions between acetazolamide and placebo group, measured by transthoracic echocardiography | Day 2 at 760m and 3200m | 
| right heart dimensions | Difference at altitude of right heart dimensions between acetazolamide and placebo group, measured by transthoracic echocardiography | Day 2 at 3200m | 
| right heart function | Difference in altitude-induced change of right heart function between acetazolamide and placebo group, measured by transthoracic echocardiography (TAPSE) | Day 2 at 760m and 3200m | 
| right heart function | Difference at altitude of right heart function between acetazolamide and placebo group, measured by transthoracic echocardiography (TAPSE) | Day 2 at 3200m | 
| stroke volume | Difference in altitude-induced change of stroke volume between acetazolamide and placebo group, measured by transthoracic echocardiography | Day 2 at 760m and 3200m | 
| stroke volume | Difference at altitude between acetazolamide and placebo group in stroke volume, measured by transthoracic echocardiography | Day 2 at 3200m | 
| volumes | Difference in altitude-induced change of volumes between acetazolamide and placebo group, measured by transthoracic echocardiography | Day 2 at 760m and 3200m | 
| volumes | Difference at altitude of volumes between acetazolamide and placebo group, measured by transthoracic echocardiography | Day 2 at 3200m | 

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