Lemborexant for Sleep and Delirium Prevention in Elderly ICU Patients

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

Interventions

DRUG

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 adjustment, and clustering of care.

DRUG

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.

Sponsors & Collaborators

• Mahidol University

  lead OTHER

Principal Investigators

• Nuanprae Kitisin · Department of Anesthesiology, Faculty of Medicine, Siriraj Hospital, Mahidol University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-01

Primary Completion

2027-07-31

Completion

2027-12-31

FDA Drug

Yes