Prochlorperazine maleate versus placebo for the prevention of acute mountain sickness: study protocol for a randomized controlled trial.

Background: Acute mountain sickness (AMS) is a debilitating condition that individuals may develop on ascent to high altitude. It is characterized by headache, nausea, vomiting, dizziness, and fatigue with the potential to progress to fatal disease. Although the pathophysiology of AMS remains unclear, proposed mechanisms are hypothesized to be similar to migraine. Prochlorperazine, a first-line treatment for acute migraine, has been shown to abort migraine early and thus may be effective in preventing AMS. Its action as a respiratory stimulant additionally makes it a promising novel agent for AMS prevention.

Methods: In this randomized double-blinded trial, participants will be randomized to receive oral prochlorperazine maleate or placebo for 24 h of three times daily dosing on a rapid ascent to 4348 m. Participants will be adults, aged 18, and older who are unacclimatized. Participants will remain at this elevation overnight. The Lake Louise Questionnaire will be utilized to define the primary outcome and presence of AMS and will be assessed the evening of and morning after ascent to peak altitude.

Discussion: Currently, acetazolamide is the preferred option for the chemoprophylaxis of AMS, which has been studied and utilized since the 1970s and involves potential prohibitive side effects. Other more efficacious options with more tolerable side effects are needed. Preventing AMS has the potential to limit both the morbidity and mortality associated with developing AMS and more serious diseases (notably high-altitude cerebral edema). Additionally, there is a substantial economic and environmental impact of AMS that could be prevented.

Trial registration: Clinicaltrial.gov, NCT06450899. Registered on June 2024.