Wright 2004b.

Methods	Design: parallel (4 arms) Country: Nepal Multisite: no International: no Treatment duration: unclear Follow up: unclear Rate of ascent (m/h): unclear Final altitude reached: 5200 m AMS scale: Lake Louise self‐reporting AMS questionnaire
Participants	24 participants enrolled. No additional information provided Exclusion criteria: not stated Participants randomized to: medroxyprogesterone group = 6 (25%); acetazolamide group = 6 (25%); acetazolamide and medroxyprogesterone group = 6 (25%); placebo group = 6 (25%). 1 participant randomized to acetazolamide was excluded from analysis, due to an unrelated illness Main characteristics of participants Age (years): range 22 to 65 years Percentage of men: 92% Body mass index: not reported
Interventions	Medroxyprogesterone group (intervention A): administration of medroxyprogesterone, 3 tablets of 10 mg twice daily Acetazolamide group (intervention B): administration of acetazolamide 250 mg twice daily + placebo, 3 tablets twice daily Acetazolamide and medroxyprogesterone group (intervention C): administration of acetazolamide 250 mg twice daily + medroxyprogesterone 3 tablets of 10 mg twice daily Placebo group (control): administration of ascorbic acid, 3 tablets of 50 mg twice daily
Outcomes	Outcomes were not pre‐defined as primary or secondary AMS incidence using Lake Louise self‐reporting AMS questionnaire AMS symptoms Blood gases Cerebral regional oxygen saturations
Notes	Trial registration: not stated Sponsor: The Wellcome Trust, the Arthur Thompson Trust, the Mount Everest foundation, Ciba Corning Diagnostics UK and Upjohn Ltd Role of sponsor: not stated A priori sample size estimation: no Conducted: not stated Declared conflicts of interest: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information to score this item as low or high risk of bias Quote: "study medications were randomized via computer‐generated code" Page 237
Allocation concealment (selection bias)	Unclear risk	Insufficient information to score this item as low or high risk of bias
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information to score this item as low or high risk of bias
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to score this item as low or high risk of bias
Incomplete outcome data (attrition bias) All outcomes	Low risk	1 participant was lost at follow‐up and not included in main analysis
Selective reporting (reporting bias)	High risk	Patient‐important outcomes, such as adverse events, were not reported
Other bias	Unclear risk	Unclear if intervention was administered before or during the ascent, or both

ACTH = adrenocorticotropic hormone; AMS = acute mountain sickness; AMS‐C = acute mountain sickness score‐ cerebral subscale; AMS‐R = acute mountain sickness score‐ respiratory subscale;BP = blood pressure; COPD = chronic obstructive pulmonary disease; Egb761 = ginkgo biloba extract EGb 761; EPO = erythropoietin; ESQ scores = environmental symptom questionnaire; FVC = forced vital capacity; GBE = Ginkgo biloba extract; g/dL = grams/decilitre; GHAQ = generalized high atitude questionnaire; HACE = high altitude cerebral oedema; HAH = high altitude headache; HAI = high altitude illness; HAPE = high altitude pulmonary oedema; ITT = intention‐to‐treat; IV = intravenous; kg = kilograms; LLS = Lake Louise scoring system;m = metres; MAP = mean artery pressure; mg = milligrams; m/h = metres/hour; NSAIDs = non‐steroidal anti‐inflammatory drugs; PASP = pulmonary artery systolic pressure; PEEP = positive end‐expiratory pressure; PEEP‐5 = 5‐cm H₂O positive end‐expiratory pressure; PEF = peak expiratory flow; PH = degree of acidity or alkalinity of a solution; RCT = randomized controlled trial; RIPC = remote ischaemic preconditioning; SD = standard deviation; SE = standard error; SEM = standard error of the mean; VAS = visual analogue scale; w‐PEEP = without PEEP