Effect Of Acetazolamide On Altitude Related Illness In Patients With Respiratory Disease

Study Overview
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Brief Summary
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Randomized, placebo controlled trial evaluating efficacy of acetazolamide in preventing altitude related adverse health effects (ARAHE) in lowlanders with chronic obstructive lung disease travelling from 760 m to 3200 m.

Detailed Description
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This is a randomized, placebo-controlled, double-blind parallel trial evaluating the efficacy of acetazolamide prophylaxis in reducing the incidence of altitude related adverse health effects (ARAHE) 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 before departure at 760 m and during the stay at altitude. Outcomes will be assessed during the stay at 3200 m. An interim analysis will be carried out when 90 patients will have completed the study or after the first year. The Peto's method will be used to correct the P-values.

Official Title
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Acetazolamide for Prevention of Altitude Related Illness in Patients With Chronic Obstructive Pulmonary Disease (COPD). Randomized, Placebo-Controlled, Double-Blind Trial.

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

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 |
| --- | --- | --- |
| Altitude related adverse health effects (ARAHE), cumulative incidence | Difference between acetazolamide and placebo group in cumulative incidence of ARAHE during the stay at 3200 m. ARAHE are defined as the following: Moderate to severe AMS (Lake Louise score ≥3 and/or Environmental Symptoms questionnaire AMSc score ≥0.7) and/or any of the following: Severe hypoxemia (SpO2 at rest <80% for >30 min or <75% for >15 min, exercise oxygen desaturation SpO2 <75% for >1 min accompanied by symptoms or signs of hypoxemia) Symptomatic cardiovascular disease (arterial blood pressure systolic >200 mmHg, diastolic >110 mmHg not responding to blood pressure lowering drugs within 1 hr; chest pain with ECG signs of ischemia or new onset arrhythmia) Withdrawal from the study by the decision of the independent physician for safetey reasons or by the patient | Day 1 to 3 at 3200m | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute mountain sickness, severity | Difference between acetazolamide and placebo group in the acute mountain sickness severity assessed by the Lake Louise questionnaire. | Day 1 to 3 at 3200m | 
| 6 min walk distance | Difference in altitude-induced change in the distance walked in 6 min between the acetazolamide and placebo group. | Day 2 at 760m and 3200m | 
| Perceived exertion | Difference in altitude-induced change in the perceived exertion rated with the Borg CR10 scale between the acetazolamide and placebo group | Day 2 at 760m and 3200m | 
| Spirometry | Difference in altitude-induced change in the spirometric variables between the acetazolamide and placebo group | Day 2 at 760m and 3200m | 
| Arterial blood gases | Difference in altitude-induced change in arterial oxygen partial pressure, carbon dioxide partial pressure, and pH between the acetazolamide and placebo group | Day 2 at 760m and 3200m | 
| Exercise endurance during constant load cycling ergometry | Difference in altitude-induced change in exercise endurance between acetazolamide and placebo group, measured by constant load cycling ergometry | Day 3 at 760m and 3200m | 
| Side effects | Difference between acetazolamide and placebo group in the cumulative incidence of medication side effects during the stay at 3200 m. | Day 1 to 3 at 3200m | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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altitude, prevention, acetazolamide, airway disease, bronchitis, emphysema