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

Acute Mountain Sickness Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03561675
• Other study ID #: 2018-01-8/305
• Status: Completed
• Phase: Phase 4
• Start date: May 15, 2018
• Est. completion date: August 31, 2019

Study information

• Verified date: May 2021
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 349
• Est. completion date: August 31, 2019
• Est. primary completion date: August 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Mountain Sickness
• Altitude Sickness

Intervention

Drug:
• ACETAZOLAMIDE oral capsule
Administration of 1x125mg acetazolamide in the morning, 2x125mg in the evening, starting 24 hours before departure to 3'100m
• Placebo oral capsule
Administration of equally looking placebo capsules in the morning and evening, starting 24 hours before departure to 3'100m

Locations

Country	Name	City	State
Kyrgyzstan	National Center of Cardiology and Internal Medicine	Bishkek

Sponsors (2)

Lead Sponsor	Collaborator
University of Zurich	National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov

Country where clinical trial is conducted

Kyrgyzstan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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