Background: Acetazolamide is the most common medication used for prevention of acute mountain sickness (AMS), a debilitating disease in those rapidly ascending to high altitude. Acetazolamide typically started the day prior to ascent, but its efficacy with day-of ascent dosing is unstudied. Our objective was to determine if day-of ascent acetazolamide prevents AMS incidence on rapid ascent to high altitude.
Methods: Double blind, randomized, controlled non-inferiority trial of acetazolamide 125 mg twice daily, started night prior to ascent (TRAD) or morning of ascent (NOVEL) to high altitude. 105 healthy adults from low altitude recruited via e-mail list-serves ascended from 1,240 m to 3,810 m summer 2018 on White Mountain, California. Primary outcome AMS incidence (Lake Louise Questionnaire [LLQ] > 3), and secondary outcomes included severe AMS incidence (LLQ > 5), overall symptom severity, and AMS incidence based on revised LLQ published 2018 (2018 AMS). To achieve 80% power, 90 participants required to detect significant difference, defined a priori as 26% difference in AMS incidence. Outcome measures analyzed using two-sample test of equal proportions and tests for differences in group central tendency.
Results: 104 participants completed the study, with well-matched characteristics (p > 0.09). 1 participant excluded post-hoc for medication non-compliance. There were 54 (52%) randomized to TRAD and 50 (48%) to NOVEL, with 95 (91%) fully compliant. Intent-to-treat (ITT) analysis showed NOVEL AMS incidence 9% greater than TRAD, but 95%CI just surpassed noninferiority margin (48.0% vs. 39%, 95%CI-12% to 30%). Severe AMS incidence non-inferior between groups but lower with NOVEL vs TRAD [5(10%) vs 12(22%), 95%CI -28 to 3.6], as were symptom severity [3.1 vs 3.5, 95%CI -0.6 to 1.3], 2018 AMS [19(38%) vs 28(52%), 95%CI -34.7 to 7], and severe 2018 AMS [5(10%) vs 6(12%), 95%CI -17.1 to 11.2]. Combined AMS incidence was 45 (43%, 95%CI 33.7-53.3) compared to 2018 AMS criteria of 47 (46%, 95%CI 35.5-55.2). All ITT outcomes were similar to compliant groups.
Conclusion: Day-of ascent acetazolamide did not demonstrate non-inferiority of AMS prevention when compared to traditional dosing, by a very small margin. As secondary outcomes were similar between groups, potential improved convenience and compliance of day-of ascent dosing may support use in high-risk populations.