Acetazolamide Add-On Therapy to OSA Surgery

NCT04227093 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: B300201942507
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Obstructive Sleep Apnea

Keywords

Acetazolamide; Carbonic anhydrase inhibitor; Upper airway stimulation; Surgery

Outcome Measures

Primary Outcomes (1)

• Apnea-hypopnea index (AHI)

  Change in AHI (events/h) from baseline to follow-up. The AHI is an index of sleep apnea severity that encompasses the frequency of apneas (cessations in breathing) and hypopneas (reductions in airflow).

  10 weeks of add-on therapy

Secondary Outcomes (6)

• Oxygen desaturation index (ODI)

  10 weeks of add-on therapy

• Oxygen saturation (SaO2)

  10 weeks of add-on therapy

• Changes in daytime sleepiness measured with the Epworth Sleepiness Scale (ESS)

  16 weeks of add-on therapy

• Changes in sleep-related quality of life measured with the Functional Outcome of Sleep Questionnaire (FOSQ-10)

  16 weeks of add-on therapy

• Changes in snoring intensity measured with a Visual Analogue Scale (VAS)

  16 weeks of add-on therapy

Study Arms (2)

Acetazolamide

ACTIVE COMPARATOR

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.

Drug: Acetazolamide

Placebo

PLACEBO COMPARATOR

The placebo regimen will be identical.

Drug: Placebo

Interventions

Acetazolamide DRUG

Oral acetazolamide tablets of 250 mg taken twice daily.

Also known as: Diamox, ATC code: S01EC01

Acetazolamide

Placebo DRUG

Matching placebo tablets taken twice daily.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Antwerp: lead

Study Sites (1)

Antwerp University Hospital

Edegem, Antwerp, 2650, Belgium

Location

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Acetazolamide

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Olivier Vanderveken, MD, PhD

  University Hospital, Antwerp

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Olivier Vanderveken, Professor and Chair Otorhinolaryngology

Model Details: Randomized, double-blind, placebo-controlled trial

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: January 13, 2020
• Study Start: January 22, 2020
• Primary Completion: April 22, 2023
• Study Completion: August 1, 2024
• Last Updated: June 18, 2024

Record last verified: 2024-06

Locations

BE (1)