Altitude Sickness Prevention With Ibuprofen Relative to Acetazolamide and Treatment Efficacy (ASPIRATE)

This double blind randomized trial will compare ibuprofen to acetazolamide for the prevention of acute mountain sickness. These drugs have never been directly compared for efficacy. 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.

Study Overview

• Status: Completed
• Conditions: Acute Mountain Sickness
• Intervention / Treatment: Drug: Ibuprofen; Drug: Acetazolamide

Detailed Description

The specific aim of this study is to evaluate if acetazolamide will be similar to ibuprofen (i.e. Ibuprofen being non-inferior) in decreasing the incidence of Acute Mountain Sickness (AMS) in travelers to high altitude. It has been shown that ibuprofen taken 3 times a day 6 hours prior to ascent is effective for the prevention of AMS, with a number needed to treat of 4, decreasing the odds of getting AMS by a third. The efficacy appears to be similar to acetazolamide, with a NNT of 3 -8, although these two medications have not been directly compared in prevention of AMS. Acetazolamide is diuretic that is the only FDA approved AMS prophylactic medication and the most commonly used drug for AMS prevention. Although acetazolamide has been given a 1A indication, it has been shown to limit exercise capabilities at high altitude, and rapid ascent has been shown to attenuate its protective effects. Ibuprofen has been given a IIB recommendation by the Wilderness Medical Society Practice Guidelines, in part because it has not directly compared to acetazolamide. It is unknown if a non-steroidal anti-inflammatory can provide protection from AMS equivalent to acetazolamide.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Bishop, California, United States, 93515
      • White Mountain Research Station

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-65 healthy non-pregnant volunteer
2. Sea-level dwelling (live at low elevation < 4000 ft)
3. Arrange your own transportation to WMRS (Bishop) by Friday evening of study weekend
4. Available for full study duration (Friday PM-Sunday AM)

Exclusion Criteria:

1. Age <18 or >65, Pregnant, Live at altitude >4000 ft
2. Slept at altitude > 4000ft within 1 week of study
3. Allergic to acetazolamide, sulfa drugs, or non-steroidal anti-inflammatories
4. Taking NSAIDs, Acetazolamide, or Corticosteroids 1 week prior to study
5. Medical History of Brain Tumor, increased brain pressure, pseudotumor cerebri, VP shunts, HACE, or HAPE.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ibuprofen; ibuprofen, 600mg, three times a day, through to ascent to high altitude	Drug: Ibuprofen; non-steroidal anti-inflammatory drug; Other Names: Motrin
Active Comparator: acetazolamide; acetazolamide, 125mg, two times a day, through to ascent to high altitude	Drug: Acetazolamide; a diuretic; Other Names: diamox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of acute mountain sickness	incidence of acute mountain sickness by Lake Louise Questionnaire	2 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
severity of acute mountain sickness	severity of acute mountain sickness by Lake Louise Questionnaire (0-15)	2 days
oxygen saturation	measurement of oxygen saturation (%) by fingertip pulse oximetry	2 days
Groningen Sleep Quality Questionnaire (GSQQ)	Groningen Sleep Quality Questionnaire (GSQQ) (0-14)	2 days

Collaborators and Investigators

• Sponsor: Grant S Lipman

Publications and helpful links

General Publications

• Burns P, Lipman GS, Warner K, Jurkiewicz C, Phillips C, Sanders L, Soto M, Hackett P. Altitude Sickness Prevention with Ibuprofen Relative to Acetazolamide. Am J Med. 2019 Feb;132(2):247-251. doi: 10.1016/j.amjmed.2018.10.021. Epub 2018 Nov 10.

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2017
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: May 11, 2017
• First Submitted That Met QC Criteria: May 12, 2017
• First Posted (Actual): May 16, 2017

Study Record Updates

• Last Update Posted (Actual): November 26, 2018
• Last Update Submitted That Met QC Criteria: November 21, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Altitude Sickness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide; Ibuprofen
• Other Study ID Numbers: 40325

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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.: No