Acute Mountain Sickness, Blood Oxygen Saturation, HeadachePhase 4NCT02244437
Ibuprofen vs Acetaminophen for AMS Prevention
A Phase 4 study testing Ibuprofen and Acetaminophen in people with Acute Mountain Sickness, Blood Oxygen Saturation, Headache, run by Mountain Medicine Society of Nepal at 1 site in Nepal.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Mountain Sickness, Blood Oxygen Saturation, Headache
- What is being tested?
- Ibuprofen and Acetaminophen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 288 participants
- Where
- 1 siteNepal
- Study dates
- Oct 2014to Dec 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Individuals not meeting inclusion criteria, including mild AMS (more than one mild symptom on the Lake Louise Questionnaire) or significantly depressed oxygen saturation (<75%); females known to be pregnant, cannot exclude the possibility of being pregnant, or have missed menses by over 7 days; individuals who have spent 24 hours at an altitude of 4500 meters/14,000 feet within the last 9 days; anyone known to have taken any of the following in the last 2 days: acetazolamide (Diamox®), steroids (dexamethasone, prednisone), theophylline, or diuretics (Lasix®); individuals who have a known intracranial space occupying lesion or a history of elevated intracranial pressure, (i.e. tumors, hydrocephalus, etc).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ibuprofen vs Acetaminophen in the Prevention of Acute Mountain Sickness: A Double Blind, Randomized Controlled Trial
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.
Read the 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.
- Being tested
- Ibuprofen, Acetaminophen
- Keywords
- altitude, altitude illnesses, headache
- Medical subject headings
- Altitude Sickness, Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbuprofenDrug
Also called 600 mg per oral three times in a day
AcetaminophenDrug
Also called 1g per oral three times in a day
| Study group | Role | What they receive |
|---|---|---|
| Ibuprofen | Active comparator | Ibuprofen has been shown to prevent AMS from previous studies. Receives: Drug: Ibuprofen |
| Acetaminophen | Experimental | Acetaminophen has not been tested yet in AMS prevention. Receives: Drug: Acetaminophen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnosis of Acute Mountain Sickness (AMS)
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.
Measured: 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.
Secondary outcomes (3)
Blood Oxygen Saturation (SPO2)
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.
Measured: 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.
Heart Rate (HR)
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.
Measured: 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.
High Altitude Headache (HAH)
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).
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2014
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Mountain Sickness, Blood Oxygen Saturation, HeadacheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 288 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mountain Medicine Society of Nepal
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Buddha Basnyat, Mountain Medicine Society of Nepal
- Investigators
- Buddha Basnyat, MD, Principal investigator, Mountain Medicine Society of Nepal (MMSN), Nepal International Clinic (NIC) and Oxford University Clinical Research Unit (OUCRU), Kathmandu, NepalMatiram Pun, MBBS/MSc/MA, Principal investigator, Mountain Medicine Society of Nepal (MMSN) and Department of Clinical Physiology, Maharajgunj Medical Campus, Institute of Medicine (IOM), Kathmandu, NepalNicholas C Kanaan, MD, Principal investigator, Department of Surgery, Division of Emergency Medicine, University of Utah, Salt Lake City, UT, USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02244437
- Sponsor's protocol ID
- 202/2013
- Status last verified
- Mar 2016
- First submitted
- 14 Sep 2014
- Last updated
- 17 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ibuprofen vs Acetaminophen in the Prevention of Acute Mountain Sickness: A Double Blind, Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02244437
- Acronym / sponsor ID
- 202/2013
- Keywords
- altitude, altitude illnesses, headache
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 288 participants (actual)
- Lead sponsor
- Mountain Medicine Society of NepalUniversity, hospital or other
- Study start
- Oct 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 19 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ibuprofen | Active comparator | Drug: IbuprofenIbuprofen has been shown to prevent AMS from previous studies. |
| Acetaminophen | Experimental | Drug: AcetaminophenAcetaminophen has not been tested yet in AMS prevention. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- Individuals not meeting inclusion criteria, including mild AMS (more than one mild symptom on the Lake Louise Questionnaire) or significantly depressed oxygen saturation (<75%); females known to be pregnant, cannot exclude the possibility of being pregnant, or have missed menses by over 7 days; individuals who have spent 24 hours at an altitude of 4500 meters/14,000 feet within the last 9 days; anyone known to have taken any of the following in the last 2 days: acetazolamide (Diamox®), steroids (dexamethasone, prednisone), theophylline, or diuretics (Lasix®); individuals who have a known intracranial space occupying lesion or a history of elevated intracranial pressure, (i.e. tumors, hydrocephalus, etc).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbuprofenAlso: 600 mg per oral three times in a day | Drug | Ibuprofen |
| AcetaminophenAlso: 1g per oral three times in a day | Drug | Acetaminophen |
Primary outcome
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.
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.
3 secondary outcomes
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.
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2016.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Buddha Basnyat, MD 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 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 principal investigator
Department of Surgery, Division of Emergency Medicine, University of Utah, Salt Lake City, UT, USA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ibuprofen and Acetaminophen in people with Acute Mountain Sickness, Blood Oxygen Saturation, Headache, run by Mountain Medicine Society of Nepal at 1 site in Nepal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Nepal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2016; AzTrials last refreshed its copy on 26 Oct 2026.