Acetazolamide to Prevent Impending Altitude-illness in Patients With COPD

Study Overview
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Brief Summary
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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
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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).

Official Title
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Novel Approach to Prevention of Altitude-related Illness in Patients With Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease, Altitude Sickness, Altitude Hypoxia

Intervention / Treatment
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* Drug: Acetazolamide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, placebo-controlled, double-blind
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Acetazolamide<br>Acetazolamide (oral capsules) | Drug: Acetazolamide<br>* 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.<br>* Other names: Acetazolamide, oral capsule;|
| Placebo Comparator: Placebo<br>Placebo (oral capsules) | Drug: Placebo<br>* 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.<br>* Other names: Placebo, oral capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of altitude-related adverse health effects | 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 | Day 1 to 3 at 3'100m | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of the individual components of altitude-related adverse health effects | Difference between participants receiving acetazolamide and placebo in the incidence and severity of components of altitude-related adverse health effects | Day 1 to 3 at 3'100m | 
| Arterial blood gases | Difference between participants receiving acetazolamide and placebo in arterial blood gases | Day 2 at 3'100 m | 
| Forced expiratory volume in one second (FEV1) | Difference between participants receiving acetazolamide and placebo in forced expiratory volume in one second (FEV1) measured by spirometry | Day 2 at 3'100 m | 
| Forced vital capacity (FVC) | Difference between participants receiving acetazolamide and placebo in forced vital capacity (FVC) measured by spirometry | Day 2 at 3'100 m | 
| Drug side effects | Difference between participants receiving acetazolamide and placebo in the incidence of drug side effects | Day 1 to 3 at 3'100m | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acetazolamide, Mountain sickness, Hypoxemia, Prevention