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

Phase 4

Completed

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Drug: ACETAZOLAMIDE oral capsule; Drug: Placebo oral capsule

• Registration Number: NCT03173508
• Lead Sponsor: University of Zurich

Brief Summary

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.

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 Timeline

• Study First Submitted: 2017-05-23
• Study Start: 2017-05-24
• Study First Submitted QC: 2017-05-31
• Study First Posted: 2017-06-01
• Primary Completion: 2018-08-02
• Study Completion: 2018-08-02
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-12
• Last Update Posted: 2019-08-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 110

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ACETAZOLAMIDE oral capsule	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
PLACEBO oral capsule	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.

Primary Outcome Measures

Name	Time	Method
pulmonary artery pressure	Day 2 at 760m and 3200m	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)

Secondary Outcome Measures

Name	Time	Method
right heart function	Day 2 at 3200m	Difference at altitude of right heart function between acetazolamide and placebo group, measured by transthoracic echocardiography (TAPSE)
volumes	Day 2 at 3200m	Difference at altitude of volumes between acetazolamide and placebo group, measured by transthoracic echocardiography
cardiac output	Day 2 at 3200m	Difference at altitude between acetazolamide and placebo group in cardiac output, measured by transthoracic echocardiography
right heart dimensions	Day 2 at 3200m	Difference at altitude of right heart dimensions between acetazolamide and placebo group, measured by transthoracic echocardiography
stroke volume	Day 2 at 3200m	Difference at altitude between acetazolamide and placebo group in stroke volume, measured by transthoracic echocardiography
pulmonary artery pressure	Day 2 at 3200m	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)

Trial Locations

Locations (1)

National Center for Cardiology and Internal Medicine; 🇰🇬 Bishkek, Kyrgyzstan