Ibuprofen vs Acetaminophen for AMS Prevention
Condition: Acute Mountain Sickness, Blood Oxygen Saturation, Headache
MeSH terms: Altitude Sickness; Headache
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Ibuprofen; Acetaminophen
Intervention type(s): Drug; Drug
Other intervention name(s): 600 mg per oral three times in a day; 1g per oral three times in a day
Intervention MeSH terms: Acetaminophen; Ibuprofen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: altitude, altitude illnesses, headache