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Sickness Evaluation at Altitude With Acetazolamide at Relative Doses (SEAWARDII)

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ClinicalTrials.gov Identifier: NCT03828474
Recruitment Status : Completed
First Posted : February 4, 2019
Last Update Posted : October 22, 2019
Sponsor:
Information provided by (Responsible Party):
Carrie Jurkiewicz, Stanford University

Brief Summary:
The specific aim of this study is to evaluate whether acetazolamide 125mg daily is no worse than acetazolamide 250mg daily in decreasing the incidence of acute mountain sickness (AMS) in travelers to high altitude. The study population is hikers who are ascending at their own rate under their own power in a true hiking environment at the White Mountain Research Station, Owen Valley Lab (OVL) and Bancroft Station (BAR), Bancroft Peak, White Mountain, California

Condition or disease Intervention/treatment Phase
Acute Mountain Sickness Drug: Acetazolamide Pill Phase 1

Detailed Description:

Acute mountain sickness (AMS) is a constellation of symptoms including headache, sleep disturbance, fatigue, dizziness, and nausea, vomiting, or anorexia that commonly occurs in travelers ascending to altitudes above 2,500m. AMS incidence varies based on altitude and ascent profile with rates reported from 25 to 75% in tourists, trekkers, and mountaineers at North American altitudes. Symptom onset is typically six to twelve hours after arrival at high altitude. This self-limited disease can be debilitating when severe, and left unrecognized or untreated may progress to potentially fatal high altitude cerebral edema (HACE). While gradual ascent has proven effective in preventing AMS, this approach is often impractical to recreationists, search and rescue, disaster relief, and military operations.

Acetazolamide increases minute ventilation by 10-20% in subjects at altitude, and hastens acclimatization. It is well established that acetazolamide's main site of action is in the kidney, where it generates a metabolic acidosis through renal bicarbonate wasting and attenuates the effects of hypoxemic-induced respiratory alkalosis. Recommended dosing of acetazolamide for AMS prophylaxis has significantly decreased since early days of use in the 1960s. The current recommended dose of acetazolamide for this indication is 125 mg twice daily, as opposed to historical recommendations of 500mg or 750mg daily. Multiple meta-analyses have concluded that when compared with higher doses, 250mg of acetazolamide daily has been shown to be equally efficacious, with the added benefit of decreasing side effects including paresthesias and dysgeusia. A randomized controlled trial confirmed effectiveness of acetazolamide 125mg twice daily in prevention of AMS when started prior to ascent. In this study, it was found that 125mg twice daily corresponded to a range of 3-5mg/kg/day, depending on subject weight. Within this range, those on the lower dosing range did not have a greater incidence or severity of AMS. For subjects weighing between 50kg (110 lbs) - 83kg (183 lbs), a dose of 250mg/day acetazolamide would fall in this range. Interestingly, mountaineers and trekkers have anecdotally reported protection against AMS with 125mg/day of acetazolamide, a dose below 3-5mg/kg for anyone over 41kg (91lb).

Finding the lowest effective dose of acetazolamide for AMS prophylaxis is important because side effects of this medication can mimic AMS, decreasing the specificity of disease scoring on the validated Lake Louise Questionnaire (LLQ) and subsequent AMS diagnosis and chemoprophylactic effectiveness.Keeping in mind that LLQ is scored based on symptoms of headache, gastrointestinal symptoms, fatigue and weakness, and dizziness and lightheadedness, whatever effect acetazolamide has on AMS prevention may be obscured by its side effects that mimic the very same disease. Falsely positive LLQ scores in trekkers and mountaineers taking acetazolamide prophylaxis may lead to unnecessary pharmacologic treatment or even evacuation. From the perspective of high altitude research, participants randomized to or already taking acetazolamide may skew study results by decreasing LLQ specificity and potentially leading researchers to overestimate incidence of AMS.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double blind randomized controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Visually identical pills
Primary Purpose: Prevention
Official Title: Sickness Evaluation at Altitude With Acetazolamide at Relative Doses
Actual Study Start Date : August 9, 2019
Actual Primary Completion Date : September 29, 2019
Actual Study Completion Date : September 29, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Acetazolamide 125mg twice daily
Acetazolamide pill 125mg twice daily by mouth, started the night prior to ascent and continued for 3 total doses
Drug: Acetazolamide Pill
Acetazolamide pill
Other Name: Diamox

Experimental: Acetazolamide 62.5mg twice daily
Acetazolamide pill 62.5mg twice daily by mouth, started the night prior to ascent and continued for 3 total doses
Drug: Acetazolamide Pill
Acetazolamide pill
Other Name: Diamox




Primary Outcome Measures :
  1. Incidence of acute mountain sickness [ Time Frame: 2 days ]
    Incidence of acute mountain sickness by Lake Louise Questionnaire



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Able to complete moderate hike at altitude
  • Live at elevation < 4,000 ft
  • Able to arrange own transportation to study site
  • Available for full study duration (Friday night - Sunday morning)

Exclusion Criteria:

  • Pregnancy
  • Slept at altitude > 4,000 ft within 1 week of study
  • Allergy to acetazolamide or sulfa drugs
  • NSAIDs, acetazolamide, or corticosteroids within 48 hours prior to study start
  • History of severe anemia, severe heart disease, advanced COPD/emphysema or sickle cell disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03828474


Locations
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United States, California
White Mountain Research Center
Bishop, California, United States, 93514
Sponsors and Collaborators
Stanford University
Investigators
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Principal Investigator: Carrie Jurkiewicz, MD Stanford University
Publications:
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Responsible Party: Carrie Jurkiewicz, Clinical Instructor, Department of Emergency Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT03828474    
Other Study ID Numbers: 49724
First Posted: February 4, 2019    Key Record Dates
Last Update Posted: October 22, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Carrie Jurkiewicz, Stanford University:
acetazolamide
chemoprophylaxis
altitude
Additional relevant MeSH terms:
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Altitude Sickness
Respiration Disorders
Respiratory Tract Diseases
Acetazolamide
Anticonvulsants
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Diuretics
Natriuretic Agents
Physiological Effects of Drugs