Effect of Acetazolamide on Right Heart Function During Exercise in Lowlanders Older Than 40 Years at Altitude

Sponsor

University of Zurich (Other)

Overall Status

Unknown status

CT.gov ID

NCT03537924

Collaborator

National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov (Other)

100

Enrollment

Location

Arms

Anticipated Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Altitude Hypoxia	Drug: ACETAZOLAMIDE oral capsule Drug: Placebo oral capsule	Phase 4

Detailed Description

This is a randomized, placebo-controlled, double-blind parallel trial evaluating the efficacy of acetazolamide prophylaxis on right heart function during exercise 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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jun 1, 2018

Anticipated Primary Completion Date :

Dec 31, 2020

Anticipated Study Completion Date :

Dec 31, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

pulmonary artery pressure (PAP) during exercise [Day 2 at 3100m]
Difference in change of tricuspid pressure gradient during exercise between acetazolamide and placebo group at altitude, measured by transthoracic echocardiography during graded cycling on an ergometer

Secondary Outcome Measures

pulmonary artery pressure during exercise [Day 2 at 760 m and 3100 m]
Difference in altitude-induced change of tricuspid pressure gradient during exercise between acetazolamide and placebo group, measured by transthoracic echocardiography during graded cycling on an ergometer
cardiac Output (CO) during exercise [Day 2 at 3100m]
Difference in change of cardiac output during exercise between acetazolamide and placebo group at altitude, measured by transthoracic echocardiography during graded cycling on an ergometer
cardiac output during exercise [Day 2 at 760 m and 3100 m]
Difference in altitude-induced change of cardiac output during exercise between acetazolamide and placebo group, measured by transthoracic echocardiography during graded cycling on an ergometer
PAP/CO slope during exercise [Day 2 at 3100m]
Difference in change of PAP/CO slope during exercise between acetazolamide and placebo group at altitude, measured by transthoracic echocardiography during graded cycling on an ergometer
PAP/CO slope during exercise [Day 2 at 760 m and 3100 m]
Difference in altitude-induced change of PAP/CO slope during exercise between acetazolamide and placebo group, measured by transthoracic echocardiography during graded cycling on an ergometer
Oxygen saturation [Day 2 at 3100m]
Difference in altitude-induced change during exercise of oxygen saturation between acetazolamide and placebo group, measured by pulse oximeter
Oxygen saturation [Day 2 at 760 m and 3100 m]
Difference in change of oxygen saturation during exercise between acetazolamide and placebo group, measured by pulse oximeter

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Center of Cardiology and Internal Medicine	Bishkek		Kyrgyzstan	720040

Sponsors and Collaborators

University of Zurich
National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov

Investigators

Study Chair: Konrad E Bloch, MD, University Hospital, Zürich
Study Director: Talant M Sooronbaev,, MD, National Center of Cardiology and Internal Medicine, Bishkek, Kyrgyzstan
Principal Investigator: Michael Furian, M, University Hospital, Zürich
Principal Investigator: Silvia Ulrich, MD, University Hospital, Zürich