Lemborexant for Sleep and Delirium Prevention in Elderly ICU Patients

NCT07407400 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: LEM-SICU
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Sleep Disturbance; Delirium; Critical Illness

Keywords

Lemborexant; Dual Orexin Receptor Antagonist; Sleep Disturbance; Delirium; Intensive Care Unit; Critically Ill Elderly

Outcome Measures

Primary Outcomes (1)

• Total Sleep Time Assessed by Actigraphy

  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.

  Nights 1-3 of the intervention period (20:00 to 08:00 each night)

Secondary Outcomes (10)

• 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)

• Composite Sleep Score Assessed by Actigraphy

  Nights 1-3 of the intervention period (20:00 to 08:00 each night).

Study Arms (2)

Lemborexant

EXPERIMENTAL

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.

Drug: Lemborexant

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Lemborexant DRUG

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 adjustment, and clustering of care.

Lemborexant

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mahidol University: lead

Related Publications (5)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Parasomnias; Delirium; Critical Illness

Interventions

lemborexant

Condition Hierarchy (Ancestors)

Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Disease Attributes; Pathologic Processes

Study Officials

• Nuanprae Kitisin

  Department of Anesthesiology, Faculty of Medicine, Siriraj Hospital, Mahidol University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nuanprae Kitisin, MD

CONTACT

+66896767706; nuanprae.kit@mahidol.ac.th

Nattaya Raykateeraroj, MD

CONTACT

+66993519963; nuanprae.kit@mahidol.ac.th

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomly assigned in a 1:1 ratio to receive either lemborexant or matching placebo. Each participant receives only one assigned intervention and is followed in parallel for study outcomes.

Study Record Dates

• First Submitted: January 29, 2026
• First Posted: February 12, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share