Acetazolamide as add-on Therapy to Obstructive Sleep Apnea Surgery (ACTOS): a Parallel-group, Double-blind, Placebo-controlled, Randomized Trial
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Apnea-hypopnea index (AHI)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Acetazolamide (Drug)
Placebo
The placebo regimen will be identical.
干预措施: Placebo (Drug)
结局指标
主要结局
Apnea-hypopnea index (AHI)
时间窗: 10 weeks of add-on therapy
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).
次要结局
- 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)
- Incidence of adverse events(16 weeks of add-on therapy)
- Oxygen desaturation index (ODI)(10 weeks of add-on therapy)
- Changes in daytime sleepiness measured with the Epworth Sleepiness Scale (ESS)(16 weeks of add-on therapy)
- Oxygen saturation (SaO2)(10 weeks of add-on therapy)
研究者
ethisch.comite@uza.be
Olivier Vanderveken, Professor and Chair Otorhinolaryngology
University Hospital, Antwerp