<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02244437</url>
  </required_header>
  <id_info>
    <org_study_id>202/2013</org_study_id>
    <nct_id>NCT02244437</nct_id>
  </id_info>
  <brief_title>Ibuprofen vs Acetaminophen for AMS Prevention</brief_title>
  <official_title>Ibuprofen vs Acetaminophen in the Prevention of Acute Mountain Sickness: A Double Blind, Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mountain Medicine Society of Nepal</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mountain Medicine Society of Nepal</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      AMS (acute mountain sickness) affects those who ascend too high (&gt;2000m) too fast.&#xD;
      Acetazolamide is an effective drug for the prevention of AMS where proper acclimatization&#xD;
      with gradual ascent may not be an option. AMS presents with headache and other non-specific&#xD;
      symptoms such as nausea, tiredness, and dizziness. Because of the side effects of&#xD;
      acetazolamide such as a tingling sensation, other drugs have been investigated to see if they&#xD;
      will prevent AMS. Ibuprofen has recently been shown to prevent AMS. In this present study the&#xD;
      investigators want to see if acetaminophen can also prevent AMS as acetaminophen unlike&#xD;
      ibuprofen does not have gastric side effects. Second, because acetaminophen has much less&#xD;
      anti-inflammatory component than ibuprofen, it may also provide some insight into the&#xD;
      pathophysiology of AMS if acetaminophen were found to be effective in the prevention of AMS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acute mountain sickness (AMS) is a well-known disorder in sojourners to high altitude&#xD;
      (&gt;2000m) characterized by headache, nausea and tiredness, akin to hangover-like symptoms. The&#xD;
      Lake Louise criteria for AMS was primarily developed to allow uniformity in comparing the&#xD;
      prevalence of AMS in different high altitude regions.&#xD;
&#xD;
      Proper acclimatization by gradual ascent to high altitude is the best means of prevention of&#xD;
      AMS. However there may be instances when rapid ascents may be necessary. Acetazolamide is the&#xD;
      best known drug for the prevention of AMS. Because of its well-known side effects like&#xD;
      tingling sensation in the fingers and toes and its potential sulpha allergy (acetazolamide is&#xD;
      a sulpha-based drug) problems, alternative drugs in the prevention of AMS have been sought.&#xD;
      Recently two randomized controlled trials have shown the usefulness of ibuprofen 600 mg tid&#xD;
      orally in the prevention of AMS.&#xD;
&#xD;
      The exact mechanism causing AMS is unknown although evidence points to a process in the&#xD;
      central nervous system. The mechanism of headache, the main feature in most AMS patients, is&#xD;
      probably multifactorial with various chemical and mechanical factors activating a final&#xD;
      common pathway, the trigeminovascular system. Triggering factors associated with high&#xD;
      altitude hypoxia leading to AMS may include arachidonic acid metabolites amongst others such&#xD;
      as serotonin, histamine, and nitric oxide. The response in AMS prevention to non-steroidal&#xD;
      anti-inflammatory drugs (NSAIDs) and steroids provides indirect evidence of arachidonic acid&#xD;
      pathway and inflammation in the genesis of AMS.&#xD;
&#xD;
      But in contrast, the role of drugs such as acetaminophen which primarily provide analgesia by&#xD;
      blunting the meningovascular receptors known to mediate nociception is unknown in the&#xD;
      prevention of AMS. Crucially if acetaminophen can prevent AMS the gastric irritation and&#xD;
      possible gastrointestinal bleeding which are well known side effects of ibuprofen would not&#xD;
      be encountered. In addition acetaminophen like ibuprofen and (unlike acetazolamide) is easily&#xD;
      available over the counter.&#xD;
&#xD;
      Therefore, the investigators hypothesize that acetaminophen in adequate dosage ( 1 g tid)&#xD;
      will be as effective as ibuprofen ( 600 mg tid) in the prevention of AMS.&#xD;
&#xD;
      Western trekkers will be randomly administered either acetaminophen or ibuprofen in a double&#xD;
      blind fashion at 4300m where the investigators will enroll the participants. Then, at 5000 m&#xD;
      at Lobuje after 48 to 96 hours the investigators will re-examine with the Lake Louise&#xD;
      Questionnaire (LLQ) to see their AMS status. The investigators will also check the pulse&#xD;
      oximeter.&#xD;
&#xD;
      Sample Size:&#xD;
&#xD;
      With a variable alpha 5%, power 80%, control 34% (based on previous studies) and experimental&#xD;
      group 18%, the sample size arrived at (using&#xD;
      http://www.sealedenvelope.com/power/binary-superiority/ ) was 115 per arm, a total of 230&#xD;
      participants. With a 20 % drop out the final number the investigators require is 288&#xD;
      participants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Diagnosis of Acute Mountain Sickness (AMS)</measure>
    <time_frame>Upon reaching 5000m altitude (Lobuche) of Nepal Himalaya. Average stay of the trekkers at this altitude is expected about a day or more. The assessment of the participants will be done next day (after spending overnight) upon their arrival.</time_frame>
    <description>AMS diagnosis will be done using Lake Louise Questionnaire (LLQ) which requires a score of three or greater with the mandatory presence of headache and at least one of the following symptoms: dizziness or light-headedness, fatigue, gastrointestinal (GI) symptoms (nausea/vomiting), or difficulty sleeping.&#xD;
LLQ is a self-report symptom questionnaire and it will be assessed among all the study participants upon arrival to the study end point i.e. 5000m altitude (Lobuche) as specified above.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Blood Oxygen Saturation (SPO2)</measure>
    <time_frame>Upon reaching 5000m altitude (Lobuche) of Nepal Himalaya. Average stay of the trekkers at this altitude is expected about a day or more. The assessment of the participants will be done next day (after spending overnight) upon their arrival.</time_frame>
    <description>Blood oxygen saturation (percentage of oxygen in the blood) among all the study participants will be measured using Pulse Oximetry. The percentage of oxygen in the blood measured will be abbreviated as SPO2 in the spreadsheet.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart Rate (HR)</measure>
    <time_frame>Upon reaching 5000m altitude (Lobuche) of Nepal Himalaya. Average stay of the trekkers at this altitude is expected about a day or more. The assessment of the participants will be done next day (after spending overnight) upon their arrival.</time_frame>
    <description>Heart rate (HR) will be assessed among all the study participants using Pulse Oximetry. The heart rate measured in the study will be abbreviated as HR in the spreadsheet.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High Altitude Headache (HAH)</measure>
    <time_frame>Upon reaching 5000m altitude (Lobuche) of Nepal Himalaya. Average stay of the trekkers at this altitude is expected about a day or more. The assessment of the participants will be done next day (after spending overnight) upon their arrival.</time_frame>
    <description>High altitude headache (HAH) and its severity will be scored based on a Visual Analog Scale (VAS) and the headache score identified on the designated LLQ score upon arrival to the study end point i.e. 5000m altitude (Lobuche).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">288</enrollment>
  <condition>Acute Mountain Sickness, Blood Oxygen Saturation, Headache</condition>
  <arm_group>
    <arm_group_label>Ibuprofen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ibuprofen has been shown to prevent AMS from previous studies.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Acetaminophen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Acetaminophen has not been tested yet in AMS prevention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibuprofen</intervention_name>
    <arm_group_label>Ibuprofen</arm_group_label>
    <other_name>600 mg per oral three times in a day</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetaminophen</intervention_name>
    <arm_group_label>Acetaminophen</arm_group_label>
    <other_name>1g per oral three times in a day</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy subjects between the ages of 18 and 65, male or female, non-Nepali, without&#xD;
             AMS or any concurrent illness, and not already taking NSAIDs and acetazolamide or any&#xD;
             other drug for the prevention of altitude illness. Subjects will be enrolled by study&#xD;
             administrators en route directly to Everest Base Camp or Kala Patthar between the&#xD;
             villages of Pheriche/Dingboche and Lobuche.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Individuals not meeting inclusion criteria, including mild AMS (more than one mild&#xD;
             symptom on the Lake Louise Questionnaire) or significantly depressed oxygen saturation&#xD;
             (&lt;75%); females known to be pregnant, cannot exclude the possibility of being&#xD;
             pregnant, or have missed menses by over 7 days; individuals who have spent 24 hours at&#xD;
             an altitude of 4500 meters/14,000 feet within the last 9 days; anyone known to have&#xD;
             taken any of the following in the last 2 days: acetazolamide (Diamox®), steroids&#xD;
             (dexamethasone, prednisone), theophylline, or diuretics (Lasix®); individuals who have&#xD;
             a known intracranial space occupying lesion or a history of elevated intracranial&#xD;
             pressure, (i.e. tumors, hydrocephalus, etc).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Buddha Basnyat, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mountain Medicine Society of Nepal (MMSN), Nepal International Clinic (NIC) and Oxford University Clinical Research Unit (OUCRU), Kathmandu, Nepal</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Matiram Pun, MBBS/MSc/MA</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mountain Medicine Society of Nepal (MMSN) and Department of Clinical Physiology, Maharajgunj Medical Campus, Institute of Medicine (IOM), Kathmandu, Nepal</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nicholas C Kanaan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Surgery, Division of Emergency Medicine, University of Utah, Salt Lake City, UT, USA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Buddha Basnyat, MD</name>
      <address>
        <city>Kathmandu</city>
        <country>Nepal</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Nepal</country>
  </location_countries>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>September 14, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2014</study_first_posted>
  <last_update_submitted>March 16, 2016</last_update_submitted>
  <last_update_submitted_qc>March 16, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 17, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mountain Medicine Society of Nepal</investigator_affiliation>
    <investigator_full_name>Buddha Basnyat</investigator_full_name>
    <investigator_title>Dr</investigator_title>
  </responsible_party>
  <keyword>altitude, altitude illnesses, headache</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Altitude Sickness</mesh_term>
    <mesh_term>Headache</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</mesh_term>
    <mesh_term>Ibuprofen</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02244437
org study id: 202/2013
nct id: NCT02244437
lead sponsor: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Diagnosis of Acute Mountain Sickness (AMS)
time frame: Upon reaching 5000m altitude (Lobuche) of Nepal Himalaya. Average stay of the trekkers at this altitude is expected about a day or more. The assessment of the participants will be done next day (after spending overnight) upon their arrival.
description: AMS diagnosis will be done using Lake Louise Questionnaire (LLQ) which requires a score of three or greater with the mandatory presence of headache and at least one of the following symptoms: dizziness or light-headedness, fatigue, gastrointestinal (GI) symptoms (nausea/vomiting), or difficulty sleeping.
LLQ is a self-report symptom questionnaire and it will be assessed among all the study participants upon arrival to the study end point i.e. 5000m altitude (Lobuche) as specified above.
measure: Blood Oxygen Saturation (SPO2)
time frame: Upon reaching 5000m altitude (Lobuche) of Nepal Himalaya. Average stay of the trekkers at this altitude is expected about a day or more. The assessment of the participants will be done next day (after spending overnight) upon their arrival.
description: Blood oxygen saturation (percentage of oxygen in the blood) among all the study participants will be measured using Pulse Oximetry. The percentage of oxygen in the blood measured will be abbreviated as SPO2 in the spreadsheet.
measure: Heart Rate (HR)
time frame: Upon reaching 5000m altitude (Lobuche) of Nepal Himalaya. Average stay of the trekkers at this altitude is expected about a day or more. The assessment of the participants will be done next day (after spending overnight) upon their arrival.
description: Heart rate (HR) will be assessed among all the study participants using Pulse Oximetry. The heart rate measured in the study will be abbreviated as HR in the spreadsheet.
measure: High Altitude Headache (HAH)
time frame: Upon reaching 5000m altitude (Lobuche) of Nepal Himalaya. Average stay of the trekkers at this altitude is expected about a day or more. The assessment of the participants will be done next day (after spending overnight) upon their arrival.
description: High altitude headache (HAH) and its severity will be scored based on a Visual Analog Scale (VAS) and the headache score identified on the designated LLQ score upon arrival to the study end point i.e. 5000m altitude (Lobuche).
arm group label: Ibuprofen
arm group type: Active Comparator
description: Ibuprofen has been shown to prevent AMS from previous studies.
arm group label: Acetaminophen
arm group type: Experimental
description: Acetaminophen has not been tested yet in AMS prevention.
intervention type: Drug
intervention name: Ibuprofen
arm group label: Ibuprofen
other name: 600 mg per oral three times in a day
intervention type: Drug
intervention name: Acetaminophen
arm group label: Acetaminophen
other name: 1g per oral three times in a day
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Buddha Basnyat, MD
role: Principal Investigator
affiliation: Mountain Medicine Society of Nepal (MMSN), Nepal International Clinic (NIC) and Oxford University Clinical Research Unit (OUCRU), Kathmandu, Nepal
last name: Matiram Pun, MBBS/MSc/MA
role: Principal Investigator
affiliation: Mountain Medicine Society of Nepal (MMSN) and Department of Clinical Physiology, Maharajgunj Medical Campus, Institute of Medicine (IOM), Kathmandu, Nepal
last name: Nicholas C Kanaan, MD
role: Principal Investigator
affiliation: Department of Surgery, Division of Emergency Medicine, University of Utah, Salt Lake City, UT, USA
facility: 
country: Nepal
responsible party type: Principal Investigator
investigator affiliation: Mountain Medicine Society of Nepal
investigator full name: Buddha Basnyat
investigator title: Dr
mesh term: Altitude Sickness
mesh term: Headache
mesh term: Acetaminophen
mesh term: Ibuprofen