Ibuprofen vs Acetaminophen for AMS Prevention

NCT ID: NCT02244437

Last Updated: 2016-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 288 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2015-12-31

Brief Summary

AMS (acute mountain sickness) affects those who ascend too high (>2000m) too fast. Acetazolamide is an effective drug for the prevention of AMS where proper acclimatization with gradual ascent may not be an option. AMS presents with headache and other non-specific symptoms such as nausea, tiredness, and dizziness. Because of the side effects of acetazolamide such as a tingling sensation, other drugs have been investigated to see if they will prevent AMS. Ibuprofen has recently been shown to prevent AMS. In this present study the investigators want to see if acetaminophen can also prevent AMS as acetaminophen unlike ibuprofen does not have gastric side effects. Second, because acetaminophen has much less anti-inflammatory component than ibuprofen, it may also provide some insight into the pathophysiology of AMS if acetaminophen were found to be effective in the prevention of AMS.

Detailed Description

Acute mountain sickness (AMS) is a well-known disorder in sojourners to high altitude (>2000m) characterized by headache, nausea and tiredness, akin to hangover-like symptoms. The Lake Louise criteria for AMS was primarily developed to allow uniformity in comparing the prevalence of AMS in different high altitude regions.

Proper acclimatization by gradual ascent to high altitude is the best means of prevention of AMS. However there may be instances when rapid ascents may be necessary. Acetazolamide is the best known drug for the prevention of AMS. Because of its well-known side effects like tingling sensation in the fingers and toes and its potential sulpha allergy (acetazolamide is a sulpha-based drug) problems, alternative drugs in the prevention of AMS have been sought. Recently two randomized controlled trials have shown the usefulness of ibuprofen 600 mg tid orally in the prevention of AMS.

The exact mechanism causing AMS is unknown although evidence points to a process in the central nervous system. The mechanism of headache, the main feature in most AMS patients, is probably multifactorial with various chemical and mechanical factors activating a final common pathway, the trigeminovascular system. Triggering factors associated with high altitude hypoxia leading to AMS may include arachidonic acid metabolites amongst others such as serotonin, histamine, and nitric oxide. The response in AMS prevention to non-steroidal anti-inflammatory drugs (NSAIDs) and steroids provides indirect evidence of arachidonic acid pathway and inflammation in the genesis of AMS.

But in contrast, the role of drugs such as acetaminophen which primarily provide analgesia by blunting the meningovascular receptors known to mediate nociception is unknown in the prevention of AMS. Crucially if acetaminophen can prevent AMS the gastric irritation and possible gastrointestinal bleeding which are well known side effects of ibuprofen would not be encountered. In addition acetaminophen like ibuprofen and (unlike acetazolamide) is easily available over the counter.

Therefore, the investigators hypothesize that acetaminophen in adequate dosage ( 1 g tid) will be as effective as ibuprofen ( 600 mg tid) in the prevention of AMS.

Western trekkers will be randomly administered either acetaminophen or ibuprofen in a double blind fashion at 4300m where the investigators will enroll the participants. Then, at 5000 m at Lobuje after 48 to 96 hours the investigators will re-examine with the Lake Louise Questionnaire (LLQ) to see their AMS status. The investigators will also check the pulse oximeter.

Sample Size:

With a variable alpha 5%, power 80%, control 34% (based on previous studies) and experimental group 18%, the sample size arrived at (using http://www.sealedenvelope.com/power/binary-superiority/ ) was 115 per arm, a total of 230 participants. With a 20 % drop out the final number the investigators require is 288 participants.

Conditions

Acute Mountain Sickness, Blood Oxygen Saturation, Headache

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Ibuprofen

Ibuprofen has been shown to prevent AMS from previous studies.

Group Type: ACTIVE_COMPARATOR

Ibuprofen

Intervention Type: DRUG

Acetaminophen

Acetaminophen has not been tested yet in AMS prevention.

Group Type: EXPERIMENTAL

Acetaminophen

Intervention Type: DRUG

Interventions

Ibuprofen

Intervention Type: DRUG

Acetaminophen

Intervention Type: DRUG

Other Intervention Names

600 mg per oral three times in a day; 1g per oral three times in a day

Eligibility Criteria

Inclusion Criteria

• Healthy subjects between the ages of 18 and 65, male or female, non-Nepali, without AMS or any concurrent illness, and not already taking NSAIDs and acetazolamide or any other drug for the prevention of altitude illness. Subjects will be enrolled by study administrators en route directly to Everest Base Camp or Kala Patthar between the villages of Pheriche/Dingboche and Lobuche.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mountain Medicine Society of Nepal

OTHER

Sponsor Role: lead

Responsible Party

Buddha Basnyat

Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Buddha Basnyat, MD

Role: PRINCIPAL_INVESTIGATOR

Mountain Medicine Society of Nepal (MMSN), Nepal International Clinic (NIC) and Oxford University Clinical Research Unit (OUCRU), Kathmandu, Nepal

Matiram Pun, MBBS/MSc/MA

Role: PRINCIPAL_INVESTIGATOR

Mountain Medicine Society of Nepal (MMSN) and Department of Clinical Physiology, Maharajgunj Medical Campus, Institute of Medicine (IOM), Kathmandu, Nepal

Nicholas C Kanaan, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Surgery, Division of Emergency Medicine, University of Utah, Salt Lake City, UT, USA

Locations

Buddha Basnyat, MD

Kathmandu, , Nepal

Countries

Nepal

Other Identifiers

202/2013

Identifier Type: -

Identifier Source: org_study_id