Effect of Acetazolamide on Right Ventricular Function at Rest in Patients With Respiratory Disease at Altitude

Effect of Acetazolamide on Right Ventricular Function at Rest in Patients With Chronic Obstructive Pulmonary Disease at Altitude. A Randomized, Placebo-controlled, Double-blind Parallel Trial

This trial will evaluate the effect of acetazolamide (375 mg per day) vs. placebo on right ventricular function at acute altitude exposure in patients with COPD.

Study Overview

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

Detailed Description

This is a randomized, placebo-controlled, double-blind parallel trial evaluating the effect of acetazolamide (375 mg per day) vs. placebo on right ventricular function at rest 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 24 hours before departure at 760 m and during the stay at altitude. Outcomes will be assessed during the stay at 3200 m.

Right ventricular function will be assessed by transthoracic echocardiography.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 4

Contacts and Locations

Study Locations

• Kyrgyzstan
  • Bishkek, Kyrgyzstan, 720040
    • National Center for 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 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 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
pulmonary artery pressure	Difference in altitude-induced change of pulmonary artery pressure (PAP) between acetazolamide and placebo group, measured by transthoracic echocardiography (tricuspid pressure gradient and pulmonary valve acceleration time)	Day 2 at 760m and 3200m

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pulmonary artery pressure	Difference at altitude of pulmonary artery pressure (PAP) between acetazolamide and placebo group, measured by transthoracic echocardiography (tricuspid pressure gradient and pulmonary valve acceleration time)	Day 2 at 3200m
cardiac output	Difference in altitude-induced change of cardiac output between acetazolamide and placebo group, measured by transthoracic echocardiography	Day 2 at 760m and 3200m
cardiac output	Difference at altitude between acetazolamide and placebo group in cardiac output, measured by transthoracic echocardiography	Day 2 at 3200m
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 3200m
right heart dimensions	Difference at altitude of right heart dimensions between acetazolamide and placebo group, measured by transthoracic echocardiography	Day 2 at 3200m
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 3200m
right heart function	Difference at altitude of right heart function between acetazolamide and placebo group, measured by transthoracic echocardiography (TAPSE)	Day 2 at 3200m
stroke volume	Difference in altitude-induced change of stroke volume between acetazolamide and placebo group, measured by transthoracic echocardiography	Day 2 at 760m and 3200m
stroke volume	Difference at altitude between acetazolamide and placebo group in stroke volume, measured by transthoracic echocardiography	Day 2 at 3200m
volumes	Difference in altitude-induced change of volumes between acetazolamide and placebo group, measured by transthoracic echocardiography	Day 2 at 760m and 3200m
volumes	Difference at altitude of volumes between acetazolamide and placebo group, measured by transthoracic echocardiography	Day 2 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 23, 2017
• First Submitted That Met QC Criteria: May 31, 2017
• First Posted (Actual): June 1, 2017

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: August 12, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: altitude; echocardiography; emphysema; acetazolamide; right ventricular function; obstructive airway disease
• 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: 2017-00137E

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