Endotype-Targeted Therapy to Rescue OSA Patients Struggling With CPAP Adherence (TOP-CPAP): a Pilot Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Mean use per night of continuous positive airway pressure (CPAP)
研究概览
简要总结
More than 10% of the US population have obstructive sleep apnea (OSA). Standard of care is therapy with CPAP (continuous positive airway pressure) which virtually eliminates OSA. However, most patients use CPAP only for part of the night (4-5hours) and about 50% patients discontinue CPAP long-term. Alternative therapies are limited, thus many OSA patients remain at risk of OSA sequelae (e.g. sleepiness, memory issues, high blood pressure, etc.). Importantly, different patients get OSA for different reasons, and recent data show that some of the underlying causes of OSA ("endotypes") such as having a low arousal threshold (i.e. waking up easily) are associated with lower CPAP adherence. Using a randomized controlled trial design, this will be the first study using a targeted intervention to manipulate the underlying OSA causes (i.e., giving a safe hypnotic to patients with OSA to increase the arousal threshold) to test the hypothesis that endotype-targeted therapy increases CPAP-adherence in patients who have low but continued CPAP usage. Ultimately, this strategy may improve the care and outcomes of millions of undertreated OSA patients.
详细描述
This double-blind, randomized, placebo-controlled, single-center, phase II trial, will test if endotype-targeted drug therapy increases CPAP adherence. Patients with low CPAP adherence (i.e. CPAP use 0.5-4h/night) will be randomized in parallel to CPAP+Eszopiclone vs CPAP+Placebo for 2 weeks. The primary outcome is mean TimeOnCPAP/night on days 2-14 after initiation of study drugs.
Aim 1: To test the effect of eszopiclone on CPAP usage in unselected OSA patients with low CPAP adherence.
Hypothesis 1: Eszopiclone improves CPAP usage more than placebo.
Aim 2: To test the effect of eszopiclone on CPAP usage in OSA patients with a low vs a high arousal threshold (ArTH) endotype.
Hypothesis 2: Eszopiclone improves CPAP usage substantially more in OSA patients with a low vs a high ArTH.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 21-65 years old
- •Body Mass Index <32 kg/m^2
- •Physician diagnosis of OSA (AHI ≥ 10) based on a clinical sleep study within the past 2 years (subjects who report a history of sleep apnea but do not have a sleep study report from the past 2 years available will be offered an overnight home sleep apnea test to verify OSA diagnosis)
- •AHI>5/h on the overnight research sleep study #1
- •Subject had the opportunity to use CPAP for at least 1 month
- •Continuous positive airway pressure (CPAP) data can be queried remotely and shows usage 0.5-4h/night (based on most recent 30 day period)
- •Interest to continue trying CPAP
排除标准
- •"SAVE CPAP Side Effect Score" >3 (1 point for each: dry mouth, nasal symptoms, CPAP pressure intolerance, claustrophobia, noise problems, soreness/skin irritation, mask fit/leak problems)
- •Any high-risk features: Epworth sleepiness score ≥18, safety-critical profession (e.g., commercial driver), prior sleep-related car accident, substantial hypoxemia during sleep [SpO2<70% for >5min] or awake [SpO2<92%]
- •Any uncontrolled medical/psychiatric condition, or safety concern based on MD judgment
- •Pregnancy/Breastfeeding (current or planned during the next month)
- •Inability to complete study procedures, such as questionnaires that are only available/validated in English
- •Other known untreated sleep fragmenting disorder, such as periodic limb movement disorder, or narcolepsy
- •Unwilling or unable to withhold CPAP during polysomnography
- •Presence of tracheostomy
- •Hospitalization within the past 90 days
- •Allergy to the study drug
- •Regular use of opioids, or benzodiazepines
- •Chronically using study drug or other hypnotic
- •Significant circadian rhythm disorder or sleepwalking as an adult
- •Active illicit substance use or >3 oz nightly alcohol use
- •Prisoners
- •Cognitive impairment, unable to provide consent, or unable to carry out research procedures
- •Safety concern based on MD judgment
研究组 & 干预措施
Eszopiclone
Subjects will be asked to take their study drugs nightly at bedtime and use their CPAP during sleep as much as possible
干预措施: Eszopiclone 2 mg (Drug)
Placebo
Subjects will be asked to take their study drugs nightly at bedtime and use their CPAP during sleep as much as possible
干预措施: Placebo (Drug)
结局指标
主要结局
Mean use per night of continuous positive airway pressure (CPAP)
时间窗: days 2-14 after initiation of study drugs
Based on device recorded usage
次要结局
- Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment (SRI) instrument(days 2-14 after initiation of study drugs)
- Response Speed(days 2-14 after initiation of study drugs)
- Alternative measures of CPAP usage(days 2-14 after initiation of study drugs)
- Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SDA) instrument(days 2-14 after initiation of study drugs)
- Epworth Sleepiness Scale (ESS)(days 2-14 after initiation of study drugs)
- Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue instrument(days 2-14 after initiation of study drugs)
- Mean Blood Pressure (mmHg)(day 14 after initiation of study drugs)
- Apnea Hypopnea Index(day1 of study drugs)
研究者
Christopher Schmickl
Assistant Professor
University of California, San Diego