Acetazolamide to Prevent Impending Altitude-illness in Patients With COPD

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Obstructive Pulmonary Disease; Altitude Sickness; Altitude Hypoxia
• Intervention / Treatment: Drug: Acetazolamide; Drug: Placebo

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).

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Acetazolamide; Acetazolamide (oral capsules)	Drug: Acetazolamide; 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.; Other Names: Acetazolamide, oral capsule
Placebo Comparator: Placebo; Placebo (oral capsules)	Drug: Placebo; 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.; Other Names: Placebo, oral capsule

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: National Center of Cardiology and Internal Medicine, Kyrgyz Republic
• Investigators: Study Chair: Konrad E Bloch, University Hospital, Zürich, Switzerland; Principal Investigator: Michael Furian, University Hospital, Zürich

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): August 10, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: May 23, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 4, 2021

Study Record Updates

• Last Update Posted (Actual): March 3, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Acetazolamide; Prevention; Hypoxemia; Mountain sickness
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Altitude Sickness; Hypoxia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: 01-2021-KEB

Drug and device information, study documents

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