Effect of Acetazolamide on Right Heart Function at Rest in Lowlanders Older Than 40 Years at Altitude.

Effect of Acetazolamide on Right Heart Function at Rest in Lowlanders Older Than 40 Years at Altitude.: A Randomized, Placebo-controlled, Double-blind Parallel Trial

Randomized, placebo controlled trial evaluating efficacy of acetazolamide on right heart function at rest in lowlanders older than 40 years travelling from 760 m to 3'100 m.

Study Overview

• Status: Active, not recruiting
• Conditions: Altitude Hypoxia
• 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 preventive acetazolamide intake on right heart function at rest in lowlanders older than 40 years 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 (3'100 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 3'100 m.

An interim analysis will be carried out when 200 participants will have completed the study and/or after the first year. The Peto's method will be used and the trial will be stopped when pre-specified futility boundaries were crossed.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• 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: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy men and women, age 40-75 yrs, without any disease and need of medication.
• Born, raised and currently living at low altitude (<800m).
• Written informed consent.
• Kyrgyz ethnicity

Exclusion Criteria:

• Any active respiratory, cardiovascular or other disease requiring regular treatment or being otherwise relevant for tolerance of hypoxia or altitude exposure.
• Any condition that may interfere with protocol compliance including current heavy smoking (>20 cigarettes per day or >20 pack-years with active smoking during the last 10 years), regular use of alcohol.
• Allergy to acetazolamide and other sulfonamides.

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 oral capsule; Acetazolamide 375mg/day (capsule @125 mg: 1 in the morning, 2 in the evening), orally. Medication starts 24 hours before ascent to 3'100m until the morning after the second night at 3'100m	Drug: ACETAZOLAMIDE oral capsule; Administration of 1x125mg acetazolamide in the morning, 2x125mg in the evening, starting 24 hours before departure to 3'100m
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 3'100m until the morning after the second night at 3'100m.	Drug: Placebo oral capsule; Administration of equally looking placebo capsules in the morning and evening, starting 24 hours before departure to 3'100m

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Difference in change of pulmonary artery pressure evaluated by echocardiography from 760 m baseline measurement to measurement at 3100 m between acetazolamide and placebo groups	Day 2 at 760m and 3100m

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in pulmonary artery pressure evaluated by echocardiography at 3100 m in the acetazolamide compared to the placebo group	Difference in pulmonary artery pressure evaluated by echocardiography at 3100 m in the acetazolamide compared to the placebo group	Day 2 at 3100m
cardiac output	Difference in altitude-induced change of cardiac output between acetazolamide and placebo group, measured by transthoracic echocardiography	Day 2 at 760m and 3100m
cardiac output	Difference at altitude between acetazolamide and placebo group in cardiac output, measured by transthoracic echocardiography	Day 2 at 3100m
right heart dimensions	Difference in altitude-induced change of right heart dimensions between acetazolamide and placebo group, measured by transthoracic echocardiography	Day 2 at 760m and 3100m
right heart dimensions	Difference at altitude of right heart dimensions between acetazolamide and placebo group, measured by transthoracic echocardiography	Day 2 at 3100m
right heart function	Difference in altitude-induced change of right heart function between acetazolamide and placebo group, measured by transthoracic echocardiography (TAPSE)	Day 2 at 760m and 3100m
right heart function	Difference at altitude of right heart function between acetazolamide and placebo group, measured by transthoracic echocardiography (TAPSE)	Day 2 at 3100m
stroke volume	Difference in altitude-induced change of stroke volume between acetazolamide and placebo group, measured by transthoracic echocardiography	Day 2 at 760m and 3100m
stroke volume	Difference at altitude between acetazolamide and placebo group in stroke volume, measured by transthoracic echocardiography	Day 2 at 3100m
volumes	Difference in altitude-induced change of volumes between acetazolamide and placebo group, measured by transthoracic echocardiography	Day 2 at 760m and 3100m
volumes	Difference at altitude of volumes between acetazolamide and placebo group, measured by transthoracic echocardiography	Day 2 at 3100m

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): June 1, 2018
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: May 15, 2018
• First Submitted That Met QC Criteria: May 28, 2018
• First Posted (Actual): May 30, 2018

Study Record Updates

• Last Update Posted (Estimate): March 10, 2023
• Last Update Submitted That Met QC Criteria: March 9, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: prevention; acetazolamide; healthy participants older than 40 years; right heart function
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; 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: 2018-01-8/305E

Drug and device information, study documents

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