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

Acetazolamide for Prevention of Altitude Related Illness in Patients With Chronic Obstructive Pulmonary Disease (COPD). Randomized, Placebo-Controlled, Double-Blind Trial.

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: ACETAZOLAMIDE oral capsule; Drug: Placebo oral capsule

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.

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 4

Contacts and Locations

Study Locations

• Kyrgyzstan
  • Bishkek, Kyrgyzstan, 720040
    • National Center of Cardiology and Internal Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: ACETAZOLAMIDE oral capsule; Acetazolamide 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	Drug: ACETAZOLAMIDE oral capsule; Administration of 125mg acetazolamide in the morning, 250mg in the evening, starting 24 hours before departure to 3200m
PLACEBO_COMPARATOR: PLACEBO oral capsule; Placebo (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.	Drug: Placebo oral capsule; Administration of equally looking placebo capsules in the morning and evening, starting 24 hours before departure to 3200m

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Altitude related adverse health effects (ARAHE), cumulative incidence	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	Day 1 to 3 at 3200m

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute mountain sickness, severity	Difference between acetazolamide and placebo group in the acute mountain sickness severity assessed by the Lake Louise questionnaire.	Day 1 to 3 at 3200m
6 min walk distance	Difference in altitude-induced change in the distance walked in 6 min between the acetazolamide and placebo group.	Day 2 at 760m and 3200m
Perceived exertion	Difference in altitude-induced change in the perceived exertion rated with the Borg CR10 scale between the acetazolamide and placebo group	Day 2 at 760m and 3200m
Spirometry	Difference in altitude-induced change in the spirometric variables between the acetazolamide and placebo group	Day 2 at 760m and 3200m
Arterial blood gases	Difference in altitude-induced change in arterial oxygen partial pressure, carbon dioxide partial pressure, and pH between the acetazolamide and placebo group	Day 2 at 760m and 3200m
Exercise endurance during constant load cycling ergometry	Difference in altitude-induced change in exercise endurance between acetazolamide and placebo group, measured by constant load cycling ergometry	Day 3 at 760m and 3200m
Side effects	Difference between acetazolamide and placebo group in the cumulative incidence of medication side effects during the stay at 3200 m.	Day 1 to 3 at 3200m

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 24, 2017
• Primary Completion (ACTUAL): August 2, 2018
• Study Completion (ACTUAL): August 2, 2018

Study Registration Dates

• First Submitted: May 15, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (ACTUAL): May 17, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 29, 2019
• Last Update Submitted That Met QC Criteria: January 26, 2019
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: altitude; prevention; emphysema; airway disease; acetazolamide; bronchitis
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: 2017-00137

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No