Altitude Hypoxia, Altitude Sickness, Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Acetazolamide, Mountain sickness, Hypoxemia, Prevention
Brief summary
The purpose of this randomized, placebo-controlled double-blind trial is to evaluate efficacy of acetazolamide in preventing overt altitude-related adverse health effects (ARAHE) in lowlanders with chronic obstructive pulmonary disease (COPD) developing early signs of altitude-illness during altitude travel.
Detailed description
This randomized placebo-controlled, double-blind, parallel-design trial will evaluate effectiveness of acetazolamide in reducing the incidence of predefined altitude-related adverse health effects in lowlanders with chronic obstructive pulmonary disease (COPD) travelling to high altitude and developping early symptoms and/or signs of impending altitude-illness. Qualifying participants will be randomized 1:1 to acetazolamide or placebo treatment during their further stay of 2 days at 3'100 m. An interim-analysis will be performed after the first year of the study or when 38 participants are randomized, whichever comes first. Symmetric stopping boundaries at P\<0.001 will be applied (Peto approach).
Interventions
DRUGAcetazolamide
Acetazolamide (oral capsules @125 mg), starting dose 3 capsules (375 mg), subsequent doses 1 capsule (125 mg) in the morning, 2 capsules (250 mg) in the evening, administered in qualifying participants, during the stay at 3100 m.
DRUGPlacebo
Placebo (oral capsules, identically looking as active drug), starting dose 3 capsules, subsequent doses 1 capsule in the morning, 2 capsules in the evening, administered in qualifying participants, during the stay at 3100 m.
Sponsors
National Center of Cardiology and Internal Medicine, Kyrgyz Republic
University of Zurich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
An independent pharmacist will prepare identically looking active and placebo capsules labelled with secret codes. Codes will be concealed to investigators and patients until completion of data analysis.
Intervention model description
randomized, placebo-controlled, double-blind
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Men and women, age 35-75 y, living at low altitude (\<800 m). * COPD diagnosed according to the Global Initiative for Obstructive Lung Disease (GOLD) guidelines, forced expiratory volume in one second 40-80% predicted, pulse oximetry ≥92%, PaCO2 \<6 kilopascal, breathing ambient air at 760 m. * One of the following early signs and/or symptoms of impending altitude-illness identified by self-monitoring during ascent to or stay at 3100 m: * Pulse oximetry SpO2≤84% * Headache or nausea/vomiting or fatigue/weakness or dizziness/light-headedness of at least moderate intensity
Exclusion criteria
* COPD exacerbation, very severe COPD with hypoxemia or hypercapnia at 760 m (see above). * Other lung disease, relevant comorbidities (such as uncontrolled cardiovascular disease, i.e., unstable arterial hypertension, coronary artery disease; previous stroke; obesity (body mass index \>35 kg/m2); internal, neurologic, rheumatologic or psychiatric disease; current heavy smoking (\>20 cigarettes per day). * Renal failure and/or allergy to sulfonamides. * Patients who do not have early signs and/or signs of impending altitude-illness by self-monitoring (as defined above) at 3'100m will not be included.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of altitude-related adverse health effects | Day 1 to 3 at 3'100m | Difference between participants receiving acetazolamide and placebo in the incidence of altitude-related adverse health effects defined as: * Moderate to severe acute mountain sickness (Lake Louise score \>4 including headache and/or Acute Mountain Sickness cerebral score ≥0.7) * Severe hypoxemia (SpO2 at rest \<80% for \>30 min; or SpO2 \<75% for \>15 min; or exercise oxygen desaturation SpO2 \<75% for \>1 min accompanied by symptoms or signs of hypoxemia) * Symptomatic cardiovascular disease (arterial blood pressure systolic \>200 mmHg, diastolic \>120 mmHg, chest pain with ECG signs of cardiac ischemia) * New onset neurologic impairment * Other intercurrent illness requiring medical treatment * Any discomfort leading to the wish of a patient to return to low altitude or withdraw from the study by the independent physician |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of the individual components of altitude-related adverse health effects | Day 1 to 3 at 3'100m | Difference between participants receiving acetazolamide and placebo in the incidence and severity of components of altitude-related adverse health effects |
| Arterial blood gases | Day 2 at 3'100 m | Difference between participants receiving acetazolamide and placebo in arterial blood gases |
| Forced expiratory volume in one second (FEV1) | Day 2 at 3'100 m | Difference between participants receiving acetazolamide and placebo in forced expiratory volume in one second (FEV1) measured by spirometry |
| Forced vital capacity (FVC) | Day 2 at 3'100 m | Difference between participants receiving acetazolamide and placebo in forced vital capacity (FVC) measured by spirometry |
| Drug side effects | Day 1 to 3 at 3'100m | Difference between participants receiving acetazolamide and placebo in the incidence of drug side effects |
Countries
Kyrgyzstan
Outcome results
None listed