Efficacy and Safety of Extended-Release Acetazolamide Capsules for the Prevention of Acute Mountain Sickness: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial.

Abstract

Danzeng, Zhuoga, Rui Zhang, Luobu Gesang, Jin Wang, Bai Ci, Zejuan Wang, Zhuoma Ciren, Quzhen Gesang, Yangzong Suona, Xiaona Liu, Quzong Zhaxi, Cuomu Baima, Binyun Liu, Zhuoga Baima, Wei Cong, and Qiangba Dingzeng. Efficacy and safety of extended-release acetazolamide capsules for the prevention of acute mountain sickness: a randomized, double-blind, placebo-controlled phase III trial. High Alt Med Biol. 00:00-00, 2025. Background: Acute mountain sickness (AMS) frequently affects individuals ascending rapidly to high altitudes. Data on acetazolamide prophylaxis in Asian populations remain limited. To evaluate the efficacy and safety of acetazolamide for the prevention of AMS in the Han Chinese population. Methods: In this multicenter, randomized, double-blind, placebo-controlled phase III trial, 288 healthy Chinese Han adults traveled from Peking (43.5 m) to Lhasa (3,670 m). Participants received either extended-release acetazolamide (500 mg once daily) or placebo, starting 2 days before ascent and continuing for 4 days postarrival. The primary endpoint was AMS incidence (Lake Louise Score [LLS] ≥3 with headache). Results: Among 284 completers, AMS incidence was significantly lower with acetazolamide (36.9% vs. 55.9%, p = 0.0013). Moderate/severe AMS (LLS > 5) was also reduced (9.9% vs. 24.5%, p = 0.0012). SpO₂ levels were consistently higher in the treatment group (p < 0.0001). Adverse events, including paresthesia and polyuria, were mild and self-limiting. Conclusion: Once-daily extended-release acetazolamide (500 mg) effectively prevents AMS and is well-tolerated in healthy Asian individuals. This regimen may enhance adherence and serve as a practical prophylactic option for high-altitude travelers.