Efficacy and Safety of a Novel Dual Orexin Receptor Antagonist in Patients With Sleep Disturbance and Hepatic Encephalopathy
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 180
- 试验地点
- 3
- 主要终点
- Percent Improvement From Baseline in Sleep Efficiency at Day 30
研究概览
简要总结
This study will evaluate the efficacy and safety of daridorexant, a dual orexin receptor antagonist, in adults with liver cirrhosis and sleep disturbance, including participants with or without covert hepatic encephalopathy. Sleep disturbance is common in people with liver cirrhosis and may affect quality of life and cognitive function. Participants will be randomly assigned to receive either daridorexant or a matching placebo for 30 days. Neither participants nor study investigators will know which treatment is assigned during the study, except when unblinding is medically necessary. Sleep and cognitive function will be assessed during the study using sleep monitoring, the Psychometric Hepatic Encephalopathy Score (PHES), and the Stroop EncephalApp, together with other clinical and laboratory assessments. The main purpose of the study is to determine whether daridorexant improves sleep efficiency compared with placebo after 30 days. The study will also evaluate changes in sleep quality, sleep structure, cognitive function, the occurrence or improvement of covert hepatic encephalopathy, and the safety of daridorexant. A total of 180 participants are planned to be enrolled at multiple participating hospitals and will be randomly assigned in a 1:1 ratio to daridorexant or placebo.
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, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-60 years.
- •Confirmed liver cirrhosis based on imaging, pathology, or clinical diagnosis.
- •Child-Pugh class A or B liver function; participants with hepatic encephalopathy must have covert hepatic encephalopathy (minimal hepatic encephalopathy [MHE]) or West-Haven grade I hepatic encephalopathy.
- •Insomnia supported by both subjective and objective evidence, including a Pittsburgh Sleep Quality Index (PSQI) total score >5 and objective polysomnography (PSG) or actigraphy findings.
- •Provision of written informed consent.
排除标准
- •Age <18 years or >60 years.
- •Child-Pugh class C liver function.
- •Overt hepatic encephalopathy of West-Haven grade II or higher.
- •Concomitant use of strong CYP3A4 inhibitors, such as itraconazole or ketoconazole, or strong CYP3A4 inducers, such as carbamazepine or rifampin.
- •Severe respiratory insufficiency or uncontrolled severe obstructive sleep apnea.
- •Pregnancy or breastfeeding.
- •Narcolepsy.
- •Known hypersensitivity to daridorexant or any of its excipients.
- •Concomitant use of central nervous system depressants, including alcohol, benzodiazepines, or opioids, that may increase sedation or somnolence.
- •Active severe psychiatric disorders, such as depression with suicidal ideation or a history of suicidal ideation, or a history of substance abuse.
- •Any contraindication to daridorexant.
研究组 & 干预措施
Placebo
Participants will receive matching placebo orally for 30 days.
干预措施: Placebo (Drug)
Daridorexant
Participants will receive daridorexant orally for 30 days. The dose will be 25 mg or 50 mg once daily according to liver function.
干预措施: Daridorexant (Drug)
结局指标
主要结局
Percent Improvement From Baseline in Sleep Efficiency at Day 30
时间窗: Baseline and Day 30
Sleep efficiency (SE) measured by overnight polysomnography (PSG). The primary endpoint is the percent improvement in sleep efficiency from baseline to Day 30.
次要结局
- Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Total Score at Day 30(Baseline and Day 30)
- Change From Baseline in Sleep Latency at Day 30(Baseline and Day 30)
- Change From Baseline in Total Sleep Time at Day 30(Baseline and Day 30)
- Change From Baseline in SWS/REM Sleep Ratio at Day 30(Baseline and Day 30)
- Change From Baseline in Microarousal Frequency at Day 30(Baseline and Day 30)
- Change in Psychometric Hepatic Encephalopathy Score (PHES)(Baseline, Day 7, Day 14, and Day 30)
- Change From Baseline in Stroop EncephalApp Performance at Day 30(Baseline and Day 30)
- Proportion of Participants With Reversal of Minimal Hepatic Encephalopathy by Day 30(Baseline through Day 30)
- Incidence of Overt Hepatic Encephalopathy by Day 30(From baseline through Day 30)
研究者
Wang Fengmei
Professor
Tianjin First Central Hospital