Acute, Intermediate and Long-term Effects of CPAP Therapy in Obstructive Sleep Apnoea: a Two-phase Interventional Trial.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Epworth Sleepines Scale Score (ESS)
研究概览
简要总结
Two-phase interventional non-inferiority trial (phase 1: at least 8 weeks of CPAP; phase 2: 2 weeks of CPAP withdrawal) including 32 patients with moderate to severe OSA to compare the physiological consequences of a short-term CPAP withdrawal to the changes in previously untreated OSA. The trial has been designed as a validation of the CPAP-withdrawal model. Baseline in-laboratory sleep studies will be performed prior to CPAP initiation, after 6-8 weeks on CPAP (treatment effect) and following 2 weeks of CPAP therapy withdrawal (withdrawal effect, effect of OSA recurrence).
详细描述
Background and Aim: Obstructive sleep apnoea (OSA) is a prevalent sleep-related breathing disorder. OSA is associated with daytime sleepiness, impaired quality of life, and adverse cardiovascular outcome. OSA can be effectively treated with nocturnal continuous positive airway pressure (CPAP) that restores normal breathing during sleep by preventing upper airway collapse. However, many patients in whom treatment of OSA is indicated are not able to adhere to CPAP, and the consequences of untreated OSA seem to differ between OSA phenotypes. Therefore, treatment alternatives to CPAP and a better understanding of treatment implications in different phenotypes of OSA are important targets in this research field. Thus, effective and controlled study designs are needed to address these research questions. Conventional randomised controlled CPAP trials are limited by low CPAP adherence resulting in an underestimation of the treatment effect. In addition, the impracticability of withholding an effective treatment from symptomatic patients resulting in inclusion of less symptomatic and patients with less severe OSA has limited the conclusions from previous trials. The CPAP therapy withdrawal model was introduced to allow studying the pathophysiological consequences of OSA and treatment effects of CPAP in an effective and controlled way. Optimally treated patients previously diagnosed with OSA established on CPAP therapy are included and undergo a short-term therapy interruption. A therapy withdrawal results in recurrence of OSA and pathophysiological changes can be attributed to OSA in this controlled model. However, it is uncertain whether the consequences of OSA during a short-term CPAP therapy withdrawal are comparable to long-term consequences of untreated OSA.
The aim of this two-phase interventional trial is to assess the effects of intermediate and long-term CPAP therapy as well as acute CPAP therapy withdrawal resulting in OSA recurrence compared to longstanding untreated OSA on cardiovascular and symptom outcomes in moderate and severe OSA. The objective is to study the comparability of conventional CPAP therapy trials with the CPAP withdrawal model in terms of evaluating relevant cardiovascular and patient-centred outcomes in OSA.
The investigators hypothesise that the treatment effect of CPAP in previously treatment-naïve patients with OSA - if adherent to CPAP - will support the same conclusions on OSA pathophysiology and therapy effects as a short-term CPAP withdrawal in treatment-adherent patients having a recurrence of OSA in response to CPAP withdrawal and thus support the use of this effective CPAP withdrawal model to use as future study design in interventional trials in OSA. It is hypothesised that the CPAP withdrawal is non-inferior to conventional CPAP trials in studying the effect on blood pressure and OSA-symptoms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Untreated moderate or severe OSA with an apnoea-hypopnoea-index (AHI) of ≥ 20/h and an oxygen desaturation index (>3%-dips) of ≥ 20/h in an in-laboratory sleep study
- •Epworth Sleepiness Scale Score ≥7/24 points
- •Indication for CPAP therapy
- •Written informed consent
排除标准
- •Moderate or more severe obstructive or restrictive ventilatory disorder (FEV1 or FVC < 70%)
- •Heart failure
- •Other types of sleep-related breathing disorders, e.g. sleep-associated hypoventilation, central sleep apnoea, Cheyne Stoke's Breathing
- •Hypoxic or hypercapnic respiratory failure (awake paO2 < 9 kPa or paCO2 > 6 kPa)
- •Active treatment for OSA (CPAP, mandibular advancement device, hypoglossal nerve stimulation)
- •Current professional driver or previous sleepiness-related accidents
- •Pregnancy
研究组 & 干预措施
Single arm (therapy initiation followed by therapy withdrawal)
Continuous positive airway pressure (CPAP)
干预措施: Continuous positive airway pressure (CPAP) (Device)
结局指标
主要结局
Epworth Sleepines Scale Score (ESS)
时间窗: at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Subjective sleepiness, ESS min-max 0-24 points and ESS \>10 indicating pathological daytime sleepiness
Nocturnal systolic blood pressure
时间窗: at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Ambulatory blood pressure monitoring (ABPM)
次要结局
- Office systolic and diastolic blood pressure(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
- 48h, 24h, diurnal, nocturnal and office heart rate(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
- Blood pressure variability (BPV, systolic and diastolic)(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
- Measures of nocturnal hypoventilation (median and maximal transcutaneous partial pressure of CO2 = tcpCO2)(at baseline and at least 8 weeks of CPAP as well as after 2 weeks of CPAP withdrawal)
- 48h, 24h, diurnal and nocturnal systolic and diastolic blood pressure(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
- Heart rate variability in the time and frequency domain (CV, RMSSD, pRR50, LF, HF, LF/HF)(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
- Measures of nocturnal hypoxaemia (time spent with SpO2 below 90% = t<90)(at baseline and at least 8 weeks of CPAP as well as after 2 weeks of CPAP withdrawal)
- Arterial stiffness(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
- Measures of nocturnal hypoxaemia (mean nocturnal oxygen saturation = ¢SpO2)(at baseline and at least 8 weeks of CPAP as well as after 2 weeks of CPAP withdrawal)
- Measures of nocturnal hypoxaemia (hypoxic burden)(at baseline and at least 8 weeks of CPAP as well as after 2 weeks of CPAP withdrawal)
- Measures of OSA severity (apnoea-hypopnoea-index)(at baseline and at least 8 weeks of CPAP as well as after 2 weeks of CPAP withdrawal)
- Urinary catecholamines(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
- Measures of OSA severity (oxygen-desaturation index)(at baseline and at least 8 weeks of CPAP as well as after 2 weeks of CPAP withdrawal)
- Baroreflex sensitivity (BRS)(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
- Sleepiness (Stanford Sleepiness Scale (SSS))(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
- Superoxide dismutase(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
- Nocturnal oxymetry measures (¢SpO2, t<90, ODI-3%, ODI-4%)(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
- Fatigue (fatigue severity scale (FSS))(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
- Disease-specific quality of life (Functional Outcomes of Sleep Questionnaire (FOSQ))(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
- Pulse rise index (>6 beats per minute)(at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal)
研究者
Esther Irene Schwarz
Deputy Clinical Director Department of Pulmonology, Principal Investigator
University of Zurich