Acetazolamide Add-On Therapy to OSA Surgery

NCT ID: NCT04227093

Last Updated: 2024-06-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-22
• Study Completion Date: 2024-08-31

Brief Summary

Surgical procedures are routinely performed as an alternative to continuous positive airway pressure treatment in patients with obstructive sleep apnea (OSA). However, the response to surgery is often variable. Instability of the respiratory control during sleep (or high loop gain) has been associated with poor surgical results in previous research. Acetazolamide (AZM), a carbonic anhydrase inhibitor, has shown potential in reducing loop gain without affecting other physiological OSA traits. In this protocol the investigators will evaluate the clinical efficacy of AZM add-on therapy to surgical procedures in patients with OSA.

Detailed Description

Seventy-four patients with diagnosed moderate to severe OSA will be equally (1:1) randomized to AZM (250 mg twice daily) or placebo add-on therapy after surgery. Two surgical procedures will be performed throughout the study: barbed reposition pharyngoplasty (BRP) and upper airway stimulation (UAS) using electrical neurostimulation of the hypoglossal nerve.

Treatment allocation will occur after a satisfactory recovery in patients undergoing BRP and after titration of the device settings in patients treated with UAS. Treatment outcome will be assessed approximately 10 weeks thereafter by in-laboratory polysomnography. Two on-site follow-up visits will be scheduled to assess adherence and adverse events. The maximum treatment duration per participant will amount to 16 weeks.

Besides the aforementioned core clinical part, the study protocol will also include an optional exploratory part prior to surgery, assessing the physiological OSA traits and airflow features by means of polysomnography and drug-induced sleep endoscopy research measurements.

Conditions

Obstructive Sleep Apnea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Acetazolamide

Acetazolamide will be prescribed in unembellished white capsules of 250 mg. The drug will be administered twice daily in the morning and evening (approximately one hour before bedtime). The total treatment length will amount to 16 weeks. In case of side effects hampering treatment adherence, the daily dosage will be reduced to a single evening dose of 250 mg.

Group Type: ACTIVE_COMPARATOR

Acetazolamide

Intervention Type: DRUG

Oral acetazolamide tablets of 250 mg taken twice daily.

Placebo

The placebo regimen will be identical.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo tablets taken twice daily.

Interventions

Acetazolamide

Oral acetazolamide tablets of 250 mg taken twice daily.

Intervention Type: DRUG

Placebo

Matching placebo tablets taken twice daily.

Intervention Type: DRUG

Other Intervention Names

Diamox; ATC code: S01EC01

Eligibility Criteria

Inclusion Criteria

• Diagnosis of moderate to severe OSA (i.e. 15≤ AHI <65 events per hour)
• Eligibility for either BRP or UAS surgery
• Fitness for general anesthesia (ASA ≤2)
• Capability of giving informed consent and willingness to undergo surgery

Exclusion Criteria

• Craniofacial anomalies affecting the UA
• Body mass index (BMI) >35 kg/m²
• General contra-indications for surgery
• Central sleep apnea (defined as central AHI ≥5 events per hour)
• Contra-indications related to acetazolamide treatment

• Hypersensitivity to sulfonamides or acetazolamide
• Renal impairment (eGFR <60 ml/min/1.73m²), electrolyte imbalances (sodium levels <135 mmol/L or potassium levels <3.5 mmol/L) and/or adrenocortical insufficiency
• Clinically significant neurological, metabolic (including diabetes mellitus type 1 or 2), hepatic (alanine transaminase or aspartate transaminase >2 times the upper limit of normal) and/or hematological disease
• Chronic obstructive pulmonary disease
• Closed-angle glaucoma
• Professional driving or handling complex machinery due to the potential risk of exaggerated daytime sleepiness
• Concomitant intake of drugs that influence breathing, sleep, arousal and/or muscle physiology
• Inability of the patient to understand and/or comply to the study procedures
• Active psychiatric disease (psychotic illness, major depression, anxiety attacks, and alcohol or drug abuse) which prevents compliance with the requirements of the research setting
• Pregnancy or willing to become pregnant

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Antwerp

OTHER

Sponsor Role: lead

Responsible Party

ethisch.comite@uza.be

Olivier Vanderveken, Professor and Chair Otorhinolaryngology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Olivier Vanderveken, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Antwerp

Locations

Antwerp University Hospital

Edegem, Antwerp, Belgium

Countries

Belgium

Other Identifiers

B300201942507

Identifier Type: -

Identifier Source: org_study_id