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Effect of Acetazolamide on Acute Mountain Sickness in Lowlanders Older Than 40 Years

Phase 4
Completed
Conditions
Acute Mountain Sickness
Interventions
Drug: Placebo oral capsule
Registration Number
NCT03561675
Lead Sponsor
University of Zurich
Brief Summary

Randomized, placebo controlled trial evaluating efficacy of acetazolamide in preventing acute mountain sickness in lowlanders older than 40 years travelling from 760 m to 3'100 m.

Detailed Description

This is a randomized, placebo-controlled, double-blind parallel trial evaluating the efficacy of acetazolamide prophylaxis in reducing the incidence of acute mountain sickness (AMS) in lowlanders older than 40 years 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 (3'100 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 3'100 m.

An interim analysis will be carried out when 80 participants will have completed the study or after the first year. The Peto's method will be used and the trial will be stopped when pre-specified futility boundaries were crossed.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
349
Inclusion Criteria
  • Healthy men and women, age 40-75 yrs, without any disease and need of medication.
  • Born, raised and currently living at low altitude (<800m).
  • Written informed consent.
  • Kyrgyz ethnicity
Exclusion Criteria
  • Any active respiratory, cardiovascular or other disease requiring regular treatment or being otherwise relevant for tolerance of hypoxia or altitude exposure.
  • Any condition that may interfere with protocol compliance including current heavy smoking (>20 cigarettes per day or >20 pack-years with active smoking during the last 10 years), regular use of alcohol.
  • Allergy to acetazolamide and other sulfonamides.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PLACEBO oral capsulePlacebo oral capsulePlacebo (capsules identically looking as acetazolamide capsules: 1 in the morning, 2 in the evening), orally. Medication starts 24 hours before ascent to 3'100m until the morning after the second night at 3'100m.
ACETAZOLAMIDE oral capsuleACETAZOLAMIDE oral capsuleAcetazolamide 375mg/day (capsule @125 mg: 1 in the morning, 2 in the evening), orally. Medication starts 24 hours before ascent to 3'100m until the morning after the second night at 3'100m
Primary Outcome Measures
NameTimeMethod
Acute mountain sickness (AMS), incidenceDay 1 to 3 at 3'100m

Difference between acetazolamide and placebo group in the incidence of AMS during the stay at 3'100 m.

Secondary Outcome Measures
NameTimeMethod
Altitude related adverse health effects (ARAHE), incidenceDay 1 to 3 at 3'100m

Difference between acetazolamide and placebo group in the incidence of ARAHE during the stay at 3'100 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 safety reasons or by the patient.

Arterial partical pressure of oxygenDay 2 at 760m and day 2 at 3'100m

Difference in altitude-induced changes in arterial partical pressure of oxygen between the acetazolamide and placebo group

Acute mountain sickness (AMS), severity assessed by the Lake Louise scoreDay 1 to 3 at 3'100m

Difference between acetazolamide and placebo group in the severity of AMS during the stay at 3'100 m. The severity of acute mountain sickness (AMS) will be assessed by the Lake Louise questionnaire (LLS), a validated questionnaire about AMS. The severity will be calculated when the presence of headache and at least one of the following symptoms is present: gastrointestinal upset, fatigue or weakness, dizziness or lightheadedness and difficulty sleeping. Each of the five questions is asked with the corresponding 0 to 3 rating of the response (0 = Not present, 1 = mild, 2 = moderate, 3 = severe). The sum of the responses on these questions is then calculated, resulting in the AMS severity.

Spirometric measurement of forced expiratory volume in one secondDay 2 at 760m and day 2 at 3'100m

Difference in altitude-induced change in the forced expiratory volume in one second between the acetazolamide and placebo group

Acute mountain sickness (AMS) at 760 m with and without acetazolamide, severityDay 3 at 760 m

Difference between acetazolamide and placebo group in the severity of AMS at 760 m.

Drug side effectsDay 1 to 3 at 3'100m

Difference between acetazolamide and placebo group in the incidence of medication side effects during the stay at 3'100 m.

Trial Locations

Locations (1)

National Center of Cardiology and Internal Medicine

🇰🇬

Bishkek, Kyrgyzstan

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