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

Acetazolamide for Prevention of Acute Mountain Sickness in Healthy Lowlanders Older Than 40 Years. Randomized Trial.

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.

Study Overview

• Status: Completed
• Conditions: Acute Mountain Sickness
• Intervention / Treatment: Drug: ACETAZOLAMIDE oral capsule; Drug: Placebo oral capsule

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.

• Study Type: Interventional
• Enrollment (Actual): 349
• Phase: Phase 4

Contacts and Locations

Study Locations

• Kyrgyzstan
  • Bishkek, Kyrgyzstan, 720040
    • National Center of Cardiology and Internal Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: ACETAZOLAMIDE oral capsule; Acetazolamide 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	Drug: ACETAZOLAMIDE oral capsule; Administration of 1x125mg acetazolamide in the morning, 2x125mg in the evening, starting 24 hours before departure to 3'100m
PLACEBO_COMPARATOR: PLACEBO oral capsule; Placebo (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.	Drug: Placebo oral capsule; Administration of equally looking placebo capsules in the morning and evening, starting 24 hours before departure to 3'100m

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute mountain sickness (AMS), incidence	Difference between acetazolamide and placebo group in the incidence of AMS during the stay at 3'100 m.	Day 1 to 3 at 3'100m

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute mountain sickness (AMS), severity assessed by the Lake Louise score	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.	Day 1 to 3 at 3'100m
Acute mountain sickness (AMS) at 760 m with and without acetazolamide, severity	Difference between acetazolamide and placebo group in the severity of AMS at 760 m.	Day 3 at 760 m
Altitude related adverse health effects (ARAHE), incidence	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.	Day 1 to 3 at 3'100m
Spirometric measurement of forced expiratory volume in one second	Difference in altitude-induced change in the forced expiratory volume in one second between the acetazolamide and placebo group	Day 2 at 760m and day 2 at 3'100m
Arterial partical pressure of oxygen	Difference in altitude-induced changes in arterial partical pressure of oxygen between the acetazolamide and placebo group	Day 2 at 760m and day 2 at 3'100m
Drug side effects	Difference between acetazolamide and placebo group in the incidence of medication side effects during the stay at 3'100 m.	Day 1 to 3 at 3'100m

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 15, 2018
• Primary Completion (ACTUAL): August 31, 2019
• Study Completion (ACTUAL): August 31, 2019

Study Registration Dates

• First Submitted: May 14, 2018
• First Submitted That Met QC Criteria: June 18, 2018
• First Posted (ACTUAL): June 19, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 13, 2021
• Last Update Submitted That Met QC Criteria: May 12, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: altitude; prevention; acetazolamide; healthy participants older than 40 years
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Altitude Sickness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: 2018-01-8/305

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No