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Effect Of Acetazolamide On Altitude Related Illness In Patients With Respiratory Disease

Phase 4
Completed
Conditions
Chronic Obstructive Pulmonary Disease (COPD)
Interventions
Drug: Placebo oral capsule
Registration Number
NCT03156231
Lead Sponsor
University of Zurich
Brief Summary

Randomized, placebo controlled trial evaluating efficacy of acetazolamide in preventing altitude related adverse health effects (ARAHE) in lowlanders with chronic obstructive lung disease travelling from 760 m to 3200 m.

Detailed Description

This is a randomized, placebo-controlled, double-blind parallel trial evaluating the efficacy of acetazolamide prophylaxis in reducing the incidence of altitude related adverse health effects (ARAHE) in lowlanders with chronic obstructive pulmonary disease travelling to altitude. Participants living in the Bishkek area, Kyrgyzstan (760m), will be transferred by car within 4h to the Tuja Ashu high altitude clinic (3200 m), and stay there for 2 days. Acetazolamide 375mg/day (or placebo), will be administered before departure at 760 m and during the stay at altitude. Outcomes will be assessed during the stay at 3200 m.

An interim analysis will be carried out when 90 patients will have completed the study or after the first year. The Peto's method will be used to correct the P-values.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
185
Inclusion Criteria
  • Male and female patients, age 18-75 yrs.
  • COPD diagnosed according to GOLD, FEV1 40-80% predicted, SpO2 ≥92% at 750 m.
  • Born, raised and currently living at low altitude (<800m).
  • Written informed consent.
Exclusion Criteria
  • COPD exacerbation, very severe COPD with hypoxemia at low altitude (FEV1/FVC <0.7, FEV1 <40% predicted, oxygen saturation on room air <92% at 750 m).
  • Comorbidities such as uncontrolled cardiovascular disease, i.e., unstable systemic arterial hypertension, coronary artery disease; previous stroke; OSA; pneumothorax in the last 2 months.
  • Internal, neurologic, rheumatologic or psychiatric disease including current heavy smoking (>20 cigarettes per day)
  • Known renal failure or allergy to acetazolamide and other sulfonamides

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ACETAZOLAMIDE oral capsuleACETAZOLAMIDE oral capsuleAcetazolamide 375mg/day (capsule @125 mg: 1 in the morning, 2 in the evening), orally. Medication starts 24 hours before ascent to 3200m until the morning after the second night at 3200m
PLACEBO oral capsulePlacebo oral capsulePlacebo (capsules identically looking as acetazolamide capsules: 1 in the morning, 2 in the evening), orally. Medication starts 24 hours before ascent to 3200m until the morning after the second night at 3200m.
Primary Outcome Measures
NameTimeMethod
Altitude related adverse health effects (ARAHE), cumulative incidenceDay 1 to 3 at 3200m

Difference between acetazolamide and placebo group in cumulative incidence of ARAHE during the stay at 3200 m.

ARAHE are defined as the following:

* Moderate to severe AMS (Lake Louise score ≥3 and/or Environmental Symptoms questionnaire AMSc score ≥0.7) and/or any of the following:

* Severe hypoxemia (SpO2 at rest \<80% for \>30 min or \<75% for \>15 min, 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 \>110 mmHg not responding to blood pressure lowering drugs within 1 hr; chest pain with ECG signs of ischemia or new onset arrhythmia)

* Withdrawal from the study by the decision of the independent physician for safetey reasons or by the patient

Secondary Outcome Measures
NameTimeMethod
Acute mountain sickness, severityDay 1 to 3 at 3200m

Difference between acetazolamide and placebo group in the acute mountain sickness severity assessed by the Lake Louise questionnaire.

6 min walk distanceDay 2 at 760m and 3200m

Difference in altitude-induced change in the distance walked in 6 min between the acetazolamide and placebo group.

Perceived exertionDay 2 at 760m and 3200m

Difference in altitude-induced change in the perceived exertion rated with the Borg CR10 scale between the acetazolamide and placebo group

SpirometryDay 2 at 760m and 3200m

Difference in altitude-induced change in the spirometric variables between the acetazolamide and placebo group

Arterial blood gasesDay 2 at 760m and 3200m

Difference in altitude-induced change in arterial oxygen partial pressure, carbon dioxide partial pressure, and pH between the acetazolamide and placebo group

Exercise endurance during constant load cycling ergometryDay 3 at 760m and 3200m

Difference in altitude-induced change in exercise endurance between acetazolamide and placebo group, measured by constant load cycling ergometry

Side effectsDay 1 to 3 at 3200m

Difference between acetazolamide and placebo group in the cumulative incidence of medication side effects during the stay at 3200 m.

Trial Locations

Locations (1)

National Center of Cardiology and Internal Medicine

🇰🇬

Bishkek, Kyrgyzstan

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