Effect of Acetazolamide on Sleep Related Breathing Disturbances in Patients With Respiratory Disease at Altitude

Effect of Acetazolamide on Sleep Related Breathing Disturbances in Patients With Chronic Obstructive Pulmonary Disease at Altitude, Assessed by Respiratory Polygraphy: A Randomized, Placebo-controlled, Double-blind Parallel Trial

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.

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 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 Type: Interventional
• Enrollment (Actual): 185
• 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: 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
Change in nocturnal oxygen saturation	Difference in altitude-induced change in mean nocturnal oxygen saturation measured by pulse oximetry between acetazolamide and placebo group	night 1 at 760m and night 1 at 3200 m
Change in nocturnal oxygen desaturation index	Difference in altitude-induced change in the mean number of cyclic dips in oxygen saturation measured by pulse oximetry between acetazolamide and placebo group	night 1 at 760m and night 1 at 3200 m

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in nocturnal oxygen saturation	Difference in altitude-induced change in mean nocturnal oxygen saturation measured by pulse oximetry between acetazolamide and placebo group	night 1 at 760m and night 2 at 3200 m
Change in nocturnal oxygen desaturation index	Difference in altitude-induced change in the mean number of cyclic dips in oxygen saturation measured by pulse oximetry between acetazolamide and placebo group	night 1 at 760m and night 2 at 3200 m
Change in apnea/hypopnea index	Difference in altitude-induced change in mean number of apneas/hypopneas per hour between the acetazolamide and placebo group	night 1 at 760m and night 1 at 3200 m
Change in apnea/hypopnea index	Difference in altitude-induced change in mean number of apneas/hypopneas per hour between the acetazolamide and placebo group	night 1 at 760m and night 2 at 3200 m
Change in subjective sleepiness and sleep quality	Difference in altitude-induced change in subjective sleepiness and sleep quality assessed by a visual analog scale between acetazolamide and placebo group	Day 1 and 2 at 760m and 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: June 5, 2017
• First Posted (Actual): June 6, 2017

Study Record Updates

• Last Update Posted (Actual): January 29, 2019
• Last Update Submitted That Met QC Criteria: January 26, 2019
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: altitude; emphysema; airway disease; acetazolamide; sleep related breathing disturbances; respiratory polygraphy; nocturnal pulse oxymetry
• 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: 2017-00137D

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