A Trial of Acetazolamide Versus Placebo in Preventing Mountain Sickness During Rapid Ascent

Study Overview
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Brief Summary
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Acute mountain sickness is a common ailment in people venturing over 2500 m altitude. Pilgrims to high altitudes are at an added risk since they are unaware and they gain height faster than the recommendations. Acetazolamide is the standard treatment and prophylaxis of acute mountain sickness. There are no randomized controlled trials that have studied protective effects of Acetazolamide in rapid ascent, and there are few conflicting studies regarding this matter. This study is a randomized, double blinded, placebo controlled trial of Acetazolamide versus placebo in 380 healthy individuals travelling to Gosaikunda Lake of Nepal in rates of ascent that are faster than the recommendations. Acetazolamide 125 mg twice daily and a placebo will be randomly assigned for 3 days and participants will be assessed at 3 stations. This study will undertake to establish the role of Acetazolamide in Rapid Ascent and will be the first RCT done in this issue. The investigators hypothesize that Acetazolamide 125mg twice daily given before rapid ascent to high altitude in Nepalese pilgrims will not be superior to placebo in decreasing both the incidence and severity of acute mountain sickness.

Official Title
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Double Blind, Placebo Controlled Randomised Trial of Acetazolamide Versus Placebo in the Prevention of Acute Mountain Sickness During Rapid Ascent

Conditions
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Acute Mountain Sickness

Intervention / Treatment
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* Drug: Acetazolamide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Nepalese national Aged 18 to 65 Travelling directly from Dhunche to Gosainkunda Rapid ascent as defined by ascent within 3 days Exclusion Criteria: Use of any drugs for the prevention of altitude sickness or headache Current illness Current altitude sickness (more than one mild symptom on the Lake Louise Questionnaire (LLQ), or oxygen saturation less than 75% Known to be pregnant or cannot exclude the possibility of being pregnant, or have missed menses by over 7 days One night within the last 30 days spent at an altitude of 4500 metres or above Residents of altitude more than 2500m A known drug allergy to sulfonamides. Treatment with any of the following in the last 2 days: acetazolamide (Diamox®), steroids (dexamethasone/decadron, prednisone), theophylline or diuretics (Lasix®), ibuprofen/motrin, naprosyn/naproxen, aspirin or acetaminophen. Any serious intracranial abnormalities such as history of brain tumours or pseudotumour cerebri Known severe uncontrolled headache syndrome Diagnosed renal function impairment, diabetes, cirrhosis of liver or liver dysfunction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Acetazolamide<br> | Drug: Acetazolamide<br>* 125 mg twice daily until 4380 meters altitude<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis of acute mountain sickness | A diagnosis of AMS requires a score of three or greater on the Lake Louise Acute Mountain Sickness Questionnaire with the mandatory presence of headache and at least one of the following symptoms: dizziness or light-headedness, fatigue, gastrointestinal (GI) symptoms (nausea/vomiting), or difficulty sleeping. | Upon reaching an altitude of 3300m, average expected time is 1 day | 
| Diagnosis of acute mountain sickness | A diagnosis of AMS requires a score of three or greater on the Lake Louise Acute Mountain Sickness Questionnaire with the mandatory presence of headache and at least one of the following symptoms: dizziness or light-headedness, fatigue, gastrointestinal (GI) symptoms (nausea/vomiting), or difficulty sleeping. | Upon reaching an altitude of 4380m, average expected time is 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood oxygen saturation | Percent | Upon reaching an altitude of 3300m, average expected time is 1 day | 
| Heart rate | Beats per minute | Upon reaching an altitude of 3300m, average expected time is 1 day | 
| High altitude headache | High altitude headache severity will be scored in milimeters based on patient markings on a visual analog scale. The headache score will be identified on the designated Lake Louise Questionnaire. | Upon reaching an altitude of 3300m, average expected time is 1 day | 
| Blood oxygen saturation | Percent | Upon reaching an altitude of 4380m, average expected time is 3 days | 
| Heart rate | Beats per minute | Upon reaching an altitude of 4380m, average expected time is 3 days | 
| High altitude headache | High altitude headache severity will be scored in millimeters based on patient markings on a visual analog scale. The headache score will be identified on the designated Lake Louise Questionnaire. | Upon reaching an altitude of 4380m, average expected time is 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute mountain sickness, Rapid ascent, High altitude headache, Mountain Medicine Society Nepal