Lemborexant for Sleep Promotion and Delirium Prevention in Critically Ill Adults: A Combined Feasibility-Pilot, Randomized, Double-Blind, Placebo-Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 100
- 主要终点
- Total Sleep Time Assessed by Actigraphy
研究概览
简要总结
Sleep disturbance is very common among critically ill patients in the intensive care unit (ICU), particularly in older adults after surgery. Poor sleep in the ICU is associated with important complications, including delirium, longer duration of mechanical ventilation, prolonged hospital stay, and increased mortality. Current non-drug approaches to improve sleep, such as reducing noise and light and clustering nursing care, may provide limited benefit and are often difficult to implement consistently. Safe and effective drug treatments for sleep in critically ill older patients remain limited.
Lemborexant is a dual orexin receptor antagonist that promotes sleep by blocking wake-promoting pathways in the brain. Unlike many traditional sleep medications, lemborexant has minimal effects on breathing and has been shown to be well tolerated in older adults with insomnia. However, its effects on sleep and delirium have not been studied in critically ill patients.
This study is a single-center, randomized, double-blind, placebo-controlled feasibility and pilot trial conducted in the surgical intensive care unit of Siriraj Hospital, Bangkok, Thailand. The study will enroll 100 critically ill postoperative patients aged 65 years or older who are expected to remain in the ICU for at least 48 hours. Participants will be randomly assigned to receive either low-dose lemborexant (2.5 mg) or a matching placebo once nightly for three consecutive nights. All participants will also receive standard non-pharmacologic sleep-promoting care used in the ICU.
The main goals of this pilot study are to evaluate the feasibility and safety of administering lemborexant in elderly ICU patients and to explore its potential effects on sleep and delirium. Sleep will be assessed using both subjective questionnaires completed each morning and objective wrist-worn actigraphy to measure sleep duration and sleep stages. Delirium will be assessed twice daily using a standardized delirium screening tool for up to seven days or until ICU discharge. Additional outcomes include medication adherence, adverse events, duration of mechanical ventilation, length of ICU and hospital stay, and in-hospital mortality.
The results of this study will provide important preliminary data on the feasibility, safety, and potential benefits of lemborexant in critically ill older adults and will help inform the design of future larger clinical trials aimed at improving sleep and reducing delirium in the ICU.
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)
盲法说明
Study medication (lemborexant and placebo) is over-encapsulated to appear identical. Participants, bedside clinical staff, investigators, outcome assessors, and data analysts are blinded to treatment allocation. Emergency unblinding is available through the hospital pharmacy if clinically required.
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 65 years or older.
- •Admission to the Surgical Intensive Care Unit (SICU).
- •Anticipated ICU stay of at least 48 hours, as assessed by the ICU consultant and responsible surgeon.
- •Able to receive enteral medication via oral or nasogastric route.
排除标准
- •Requirement for frequent neurological checks or scheduled awakening (e.g., acute stroke or neurosurgery).
- •Deep sedation defined as Richmond Agitation-Sedation Scale (RASS) ≤ -
- •Positive Confusion Assessment Method for the ICU (CAM-ICU) within 12 hours prior to randomization.
- •Severe hemodynamic or respiratory instability requiring neuromuscular blockers or high-dose vasopressors (e.g., norepinephrine ≥ 0.1 µg/kg/min and titrating upward).
- •High risk of aspiration, including ongoing vomiting, gastric residual volume >250 mL, or intolerance to oral or enteral medications.
- •Concomitant use of strong CYP3A inhibitors or inducers (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, rifampicin, carbamazepine, phenytoin, or St. John's wort).
- •Severe hepatic impairment (Child-Pugh class C).
- •End-stage kidney disease or chronic kidney disease stage
- •Concomitant use of sedative-hypnotic medications, including benzodiazepines, Z-drugs, trazodone, tricyclic antidepressants, melatonin, or other sleep-inducing agents.
- •Known hypersensitivity to lemborexant or other dual orexin receptor antagonists.
- •History of cataplexy-like symptoms or severe depression with suicidal ideation.
研究组 & 干预措施
Lemborexant
Participants receive lemborexant 2.5 mg (half of a 5-mg tablet) administered orally or via nasogastric tube once nightly at 20:00 ± 30 minutes for three consecutive nights. All participants also receive standard non-pharmacologic sleep-promoting care in the ICU.
干预措施: Lemborexant (Drug)
Placebo
Participants receive a matching placebo administered orally or via nasogastric tube once nightly at 20:00 ± 30 minutes for three consecutive nights. All participants also receive standard non-pharmacologic sleep-promoting care in the ICU.
干预措施: Placebo (Drug)
结局指标
主要结局
Total Sleep Time Assessed by Actigraphy
时间窗: Nights 1-3 of the intervention period (20:00 to 08:00 each night)
Total sleep time (TST) measured using wrist-worn actigraphy (Fitbit Charge 5), defined as the total number of minutes scored as sleep during the nighttime period.
次要结局
- Subjective Sleep Quality Assessed by Richards-Campbell Sleep Questionnaire(Each morning after Nights 1-3 of the intervention period (approximately 08:00))
- Delirium Incidence Assessed by CAM-ICU(From randomization until ICU Day 7 or ICU discharge, whichever occurs first)
- Delirium Duration(From randomization until ICU Day 7 or ICU discharge, whichever occurs first)
- Objective Sleep Stage Proportions Assessed by Actigraphy(Nights 1-3 of the intervention period (20:00 to 08:00 each night))
- Completion Rate of Subjective Sleep Assessments(Each morning after Nights 1-3 of the intervention period (approximately 08:00).)
- Composite Sleep Score Assessed by Actigraphy(Nights 1-3 of the intervention period (20:00 to 08:00 each night).)
- Safety and Adverse Events(From the first dose of study medication until ICU discharge, assessed for up to 7 days after randomization, whichever occurs first.)
- Recruitment Rate(During the recruitment period, from first patient screened to last patient randomized.)
- Medication Adherence to Study Drug(Nights 1-3 of the intervention period)
- Adequacy of Actigraphy Wear Time(Nights 1-3 of the intervention period (20:00 to 08:00 each night).)