Effect of Acetazolamide on Right Heart Function at Rest in Lowlanders With COPD Traveling to High Altitude

Effect of Acetazolamide on Right Heart Function at Rest in Lowlanders With Chronic Obstructive Pulmunary Disease (COPD) Traveling to High Altitude

The purpose of this randomized, placebo-controlled double-blind trial is to evaluate the effect of acetazolamide on right heart function at rest in lowlanders with chronic obstructive pulmonary disease (COPD) traveling to high altitude (HA) and developing early signs of altitude-illness.

Study Overview

• Status: Recruiting
• Conditions: Chronic Obstructive Pulmonary Disease; Altitude Sickness; Right Heart Function
• Intervention / Treatment: Drug: Acetazolamide; Drug: Placebo

Detailed Description

This randomized placebo-controlled, double-blind, parallel-design trial will evaluate effect of acetazolamide on right heart function 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.

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

Contacts and Locations

• Study Contact: Name: Silvia Ulrich, Prof; Phone Number: +41442552220; Email: silvia.ulrich@usz.ch
• Study Contact Backup: Name: Konrad E. Bloch, Prof; Phone Number: +41442553828; Email: konrad.bloch@usz.ch

Study Locations

• Kyrgyzstan
  • Bishkek, Kyrgyzstan, 720040
    • Recruiting
    • National Center of Cardiology and Internal Medicine
    • Contact: Talant M Sooronbaev, MD

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, FEV1 40-80% predicted, pulse oximetry

  ≥92%, PaCO2 <6 kPa, breathing ambient air at 760 m.

• One of the following early signs and/or symptoms of impending altitudeillness 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/lightheadedness 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 altitudeillness 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: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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, 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.	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
Difference in change of pulmonary artery pressure	Difference in change of pulmonary artery pressure (RV/RA) evaluated by echocardiography at 3100 m in the acetazolamide compared to the placebo group	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in change of pulmonary artery pressure (RV/RA) low altitude versus high altitude	Difference in change of pulmonary artery pressure evaluated by echocardiography from 760 m baseline measurement to measurement at 3100 m in the acetazolamide compared to the placebo group	3 days
Difference in cardiac output	Difference in change of cardiac output evaluated by echocardiography in the acetazolamide compared to the placebo group	3 days
Difference in right heart dimensions	Difference in change of right heart dimensions evaluated by echocardiography in the acetazolamide compared to the placebo group	3 days
Difference in right heart function	Difference in change of tricuspid annular plane systolic sxcursion (TAPSE) evaluated by echocardiography in the acetazolamide compared to the placebo group	3 days
Difference in right heart function	Difference in change of fraction area change (FAC) evaluated by echocardiography in the acetazolamide compared to the placebo group	3 days
Difference in right heart function	Difference in change of tissue dopple S (TDI S) evaluated by echocardiography in the acetazolamide compared to the placebo group	3 days

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: National Center of Cardiology and Internal Medicine, Kyrgyz Republic
• Investigators: Study Chair: Silvia Ulrich, Prof, University Hospital, Zürich, Switzerland

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: May 31, 2021
• First Submitted That Met QC Criteria: May 31, 2021
• First Posted (Actual): June 7, 2021

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: November 1, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Acetazolamide; Pulmonary Hypertension; Mountain sickness
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Altitude Sickness; 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-SU-HAECHO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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