The SPironolactone and ACEtazolamide (SPACE) trial in the prevention of acute mountain sickness

ISRCTN	ISRCTN77054547
DOI	https://doi.org/10.1186/ISRCTN77054547
Protocol serial number	OXTREC 1
Sponsor	University of Oxford (UK)
Funder	Oxford University Clinical Research Unit (Vietnam) (ref: HB0075)

Submission date: 30/07/2007
Registration date: 04/09/2007
Last edited: 24/11/2008

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Signs and Symptoms

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Buddha Basnyat
Scientific

Nepal International Clinic
Lal Durbar
GPO BOX 3596
Kathmandu
1
Nepal

Email	rishibas@wlink.com.np

Study information

Primary study design	Interventional
Study design	Randomised, double blind, placebo controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title
Study acronym	SPACE
Study objectives	Acute Mountain Sickness (AMS) is like a hangover (headache, nausea and tiredness being prominent features) that may manifest at altitudes greater than 2600 m when people ascend too high too fast. This is a study to ascertain the benefit of spironolactone (aldactone), a water pill, in the prevention of AMS which comprises of headache, nausea and tiredness at altitude greater than 2700 m. Acetazolamide (Diamox®) which we know works for the prevention of AMS will be compared with spironolactone and a placebo or a sugar pill. Hypothesis: Spironolactone will prevent AMS.
Ethics approval(s)	Added 24/11/2008: OXTREC approval on 07/10/2008 for the study (031 07).
Health condition(s) or problem(s) studied	Acute mountain sickness
Intervention	This is a prospective three armed, double blind, randomised, placebo controlled trial. Computer generated randomisation of spironolatone, acetazolamide and placebo will be carried out. After consent is obtained, participants will receive a four days supply of either spironolactone 50 mg twice daily (bid), acetazolamide 250 mg bid or visually matched placebo bid. Trekkers will be enrolled in the study and baseline measurements done at Pheriche (4300 m) and reassessed after their arrival at the endpoint in Lobuje (5000 m). The reassessment will take place at least 36 hours to a maximum of 96 hours (4 days) after taking the study drug. Assessments and measurements will be made in these areas prior to and after ascension on the study drug: 1. Lake Louise Questionnaire 2. Oxygen saturation via pulse oximetry The approach to Everest Base Camp provides a unique study population for the following reasons: 1. Large numbers of recently arrived (non-acclimated) trekkers 2. Relatively homogenous population (gender, age, physical fitness, etc.) with relatively few pre-existing conditions 3. Linear population movement along the approach 4. Rapid and quantitatively large elevation change (about 700 m) Data will also be collected on the demographics of the study population at the enrolment site. The study will not provide financial assistance in the event of the development of complications of being at high altitude.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Spironolactone, acetazolamide
Primary outcome measure(s)	Main outcome measure will be incidence of AMS measured by Lake Louise acute mountain sickness score (LLscore) greater than or equal to three with headache and at least one other symptom. Outcomes will be measured at baseline (Pheriche 4300 m) and remeasured at Lobuje (5000 m). The reassessment will take place at least 36 hours to a maximum of 96 hours (four days) after taking the study drug.
Key secondary outcome measure(s)	1. Oxygen saturation measured by pulse oximeter 2. Severity of symptom (LLscore greater than five) 3. Incidence of headache and severity of headache Outcomes will be measured at baseline (Pheriche 4300 m) and remeasured at Lobuje (5000 m). The reassessment will take place at least 36 hours to a maximum of 96 hours (four days) after taking the study drug.
Completion date	25/11/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Not Specified
Target sample size at registration	300
Key inclusion criteria	1. Healthy subjects between the ages of 18 and 65 2. Male or female 3. Non-Nepali 4. Without AMS or any concurrent illness 5. Not already taking 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 Lobuje.
Key exclusion criteria	1. Individuals not meeting inclusion criteria, including mild AMS (more than one mild symptom on the Lake Louise Questionnaire) or significantly depressed oxygen saturation (less than 75%) 2. Females known to be pregnant, or cannot exclude the possibility of being pregnant, or have missed menses by over seven days 3. Individuals with a known drug allergy to acetazolamide or other sulfa drugs 4. Individuals who are on Angiotensin-Converting Enzyme (ACE) inhibitors (like enalapril) or other diuretics like amiloride or triamterene, as concurrent administration with spironolactone can cause hyperkalemia 5. Individuals who have spent 24 hours at an altitude of 4500 metres/14,000 feet within the last nine days 6. Anyone known to have taken any of the following in the last two days: 6.1. Acetazolamide (Diamox®) 6.2. Steroids (dexamethasone, prednisone) 6.3. Theophylline 6.4. Diuretics (Lasix®) 7. Individuals who have a known intracranial space occupying lesion or a history of elevated intracranial pressure, (i.e. tumours, hydrocephalus, etc) 8. Lack of informed consent will obviously mandate exclusion
Date of first enrolment	10/10/2007
Date of final enrolment	25/11/2007

Locations

Countries of recruitment

Nepal

Study participating centre

Nepal International Clinic

Kathmandu
1
Nepal

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes