Effect of Acetazolamide on Sleep Related Breathing Disturbances 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: NCT03177850
• Lead Sponsor: University of Zurich

Brief Summary

In this trial, the investigators will evaluate the effect of acetazolamide (375 mg per day) vs. placebo on sleep related breathing disturbances at altitude 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 sleep related breathing disturbances 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.

Sleep related breathing disturbances will be evaluated by respiratory polygraphy.

An interim analysis will be carried out when 90 patients will have completed the study or after the first year. The Peto's method will be used to correct the P-values.

Study Timeline

• Study First Submitted: 2017-05-23
• Study Start: 2017-05-24
• Study First Submitted QC: 2017-06-05
• Study First Posted: 2017-06-06
• Status Verified: 2017-10
• Primary Completion: 2018-08-02
• Study Completion: 2018-08-02
• Last Update Submitted: 2019-01-26
• Last Update Posted: 2019-01-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 185

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
Change in nocturnal oxygen saturation	night 1 at 760m and night 1 at 3200 m	Difference in altitude-induced change in mean nocturnal oxygen saturation measured by pulse oximetry between acetazolamide and placebo group
Change in nocturnal oxygen desaturation index	night 1 at 760m and night 1 at 3200 m	Difference in altitude-induced change in the mean number of cyclic dips in oxygen saturation measured by pulse oximetry between acetazolamide and placebo group

Secondary Outcome Measures

Name	Time	Method
Change in nocturnal oxygen desaturation index	night 1 at 760m and night 2 at 3200 m	Difference in altitude-induced change in the mean number of cyclic dips in oxygen saturation measured by pulse oximetry between acetazolamide and placebo group
Change in apnea/hypopnea index	night 1 at 760m and night 2 at 3200 m	Difference in altitude-induced change in mean number of apneas/hypopneas per hour between the acetazolamide and placebo group
Change in subjective sleepiness and sleep quality	Day 1 and 2 at 760m and 3200m	Difference in altitude-induced change in subjective sleepiness and sleep quality assessed by a visual analog scale between acetazolamide and placebo group
Change in nocturnal oxygen saturation	night 1 at 760m and night 2 at 3200 m	Difference in altitude-induced change in mean nocturnal oxygen saturation measured by pulse oximetry between acetazolamide and placebo group

Trial Locations

Locations (1)

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