Randomized, placebo controlled trial evaluating the effect of acetazolamide on lung water content by ultrasound in lowlanders older than 40 years travelling from 760 m to 3'100 m.

This is a randomized, placebo-controlled, double-blind parallel trial evaluating the effect of preventive acetazolamide intake on lung water content by ultrasound 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 200 participants will have completed the study and/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.

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.