Lemborexant for Sleep and Delirium Prevention in Elderly ICU Patients

Официальное название

Lemborexant for Sleep Promotion and Delirium Prevention in Critically Ill Adults: A Combined Feasibility-Pilot, Randomized, Double-Blind, Placebo-Controlled Trial

Обзор

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.

Вмешательства

• Препарат Lemborexant
  Lemborexant is administered at a dose of 2.5 mg (half of a 5-mg tablet) once nightly at 20:00 ± 30 minutes for three consecutive nights. The medication is given orally or via nasogastric tube. For nasogastric administration, the tablet is crushed, mixed with sterile water, and flushed through the tube. Lemborexant is over-encapsulated to maintain blinding. All participants also receive standard non-pharmacologic sleep-promoting care in the ICU, including light reduction, noise and alarm adjustme
• Препарат Placebo
  A matching inert placebo tablet/capsule identical in appearance to lemborexant is administered orally or via nasogastric tube once nightly at 20:00 ± 30 minutes for three consecutive nights. The placebo is over-encapsulated to maintain blinding. All participants receive standard non-pharmacologic sleep-promoting care in the ICU, including light reduction, noise and alarm adjustment, and clustering of care.

Первичные конечные точки

• Total Sleep Time Assessed by Actigraphy [Срок оценки: Nights 1-3 of the intervention period (20:00 to 08:00 each night)]

Вторичные конечные точки (10)

• Subjective Sleep Quality Assessed by Richards-Campbell Sleep Questionnaire [Срок оценки: Each morning after Nights 1-3 of the intervention period (approximately 08:00)]
• Delirium Incidence Assessed by CAM-ICU [Срок оценки: From randomization until ICU Day 7 or ICU discharge, whichever occurs first]
• Delirium Duration [Срок оценки: From randomization until ICU Day 7 or ICU discharge, whichever occurs first]
• Objective Sleep Stage Proportions Assessed by Actigraphy [Срок оценки: Nights 1-3 of the intervention period (20:00 to 08:00 each night)]
• Composite Sleep Score Assessed by Actigraphy [Срок оценки: Nights 1-3 of the intervention period (20:00 to 08:00 each night).]
• Safety and Adverse Events [Срок оценки: From the first dose of study medication until ICU discharge, assessed for up to 7 days after randomization, whichever occurs first.]
• Recruitment Rate [Срок оценки: During the recruitment period, from first patient screened to last patient randomized.]
• Medication Adherence to Study Drug [Срок оценки: Nights 1-3 of the intervention period]
• Completion Rate of Subjective Sleep Assessments [Срок оценки: Each morning after Nights 1-3 of the intervention period (approximately 08:00).]
• Adequacy of Actigraphy Wear Time [Срок оценки: Nights 1-3 of the intervention period (20:00 to 08:00 each night).]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• Requirement for frequent neurological checks or scheduled awakening (e.g., acute stroke or neurosurgery).
• Deep sedation defined as Richmond Agitation-Sedation Scale (RASS) ≤ -3.
• 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 5.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Kitisin N, Somnuke P, Thikom N, Raykateeraroj N, Poontong N, Thanakiattiwibun C, Wongtangman K. Psychometric properties of a Thai version of the Richards-Campbell sleep questionnaire. Nurs Crit Care. 2022 Nov;27(6):885-892. doi: 10.1111/nicc.12705. Epub 2021 Aug 23. PMID 34425024
• Tilouche N, Hassen MF, Ali HBS, Jaoued O, Gharbi R, El Atrous SS. Delirium in the Intensive Care Unit: Incidence, Risk Factors, and Impact on Outcome. Indian J Crit Care Med. 2018 Mar;22(3):144-149. doi: 10.4103/ijccm.IJCCM_244_17. PMID 29657370
• Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. doi: 10.1001/jama.291.14.1753. PMID 15082703
• Drouot X, Cabello B, d'Ortho MP, Brochard L. Sleep in the intensive care unit. Sleep Med Rev. 2008 Oct;12(5):391-403. doi: 10.1016/j.smrv.2007.11.004. Epub 2008 May 23. PMID 18502155
• Parthasarathy S, Tobin MJ. Sleep in the intensive care unit. Intensive Care Med. 2004 Feb;30(2):197-206. doi: 10.1007/s00134-003-2030-6. Epub 2003 Oct 16. PMID 14564378

Идентификаторы

NCT: NCT07407400 · LEM-SICU

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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