Lemborexant for Sleep and Delirium Prevention in Elderly ICU Patients

Phase 4Not Yet RecruitingNCT07407400

Mahidol University100 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Interventions

LemborexantDRUG

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.

PlaceboDRUG

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.

Eligibility

Sex: ALLMin age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Outcomes

Primary Outcomes

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.

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

Secondary Outcomes

Subjective Sleep Quality Assessed by Richards-Campbell Sleep Questionnaire

Subjective Sleep Quality Assessed by the Richards-Campbell Sleep Questionnaire (RCSQ). Subjective sleep quality will be assessed using the validated Thai version of the Richards-Campbell Sleep Questionnaire. The RCSQ consists of five items (sleep depth, sleep latency, number of awakenings, efficiency of returning to sleep, and overall sleep quality), each rated on a visual analogue scale ranging from 0 to 50 mm, where 0 represents the poorest sleep and 50 represents the best sleep. The total RCSQ score is calculated as the mean of the five item scores, yielding a composite score ranging from 0 to 50, with higher scores indicating better subjective sleep quality.

Time frame: Each morning after Nights 1-3 of the intervention period (approximately 08:00)

Delirium Incidence Assessed by CAM-ICU

Delirium incidence will be assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), a validated diagnostic instrument for delirium in critically ill patients. The CAM-ICU is not a continuous or ordinal scale but a binary diagnostic assessment, yielding either a positive (delirium present) or negative (delirium absent) result based on four core features (acute change or fluctuating course, inattention, altered level of consciousness, and disorganized thinking). Delirium incidence is defined as the occurrence of at least one positive CAM-ICU assessment during the observation period. As this outcome is dichotomous, minimum and maximum scale values are not applicable, and higher or lower scores do not represent better or worse outcomes.

Time frame: From randomization until ICU Day 7 or ICU discharge, whichever occurs first

Delirium Duration

Delirium duration defined as the total number of days with a positive CAM-ICU assessment during the observation period.

Time frame: From randomization until ICU Day 7 or ICU discharge, whichever occurs first

Objective Sleep Stage Proportions Assessed by Actigraphy

Objective sleep architecture will be assessed using wrist-worn actigraphy (Fitbit Charge 5). Sleep stage proportions, including deep sleep, light sleep, and rapid eye movement (REM) sleep, will be derived from actigraphy algorithms and expressed as the percentage (%) of total sleep time for each night. Each sleep stage proportion ranges from 0% to 100%, where higher values indicate a greater proportion of time spent in that specific sleep stage. No composite or total score is calculated for this outcome.

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

Composite Sleep Score Assessed by Actigraphy

Overall objective sleep quality will be assessed using the composite sleep score generated by wrist-worn actigraphy (Fitbit Charge 5). The composite sleep score is a proprietary summary metric derived from multiple actigraphy-based parameters, including sleep duration, continuity, and sleep stage distribution. The composite sleep score ranges from 0 to 100, where higher scores indicate better overall objective sleep quality.

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

Safety and Adverse Events

Safety will be assessed by the frequency and nature of adverse events (AEs) and serious adverse events (SAEs) potentially related to the study medication. Prespecified events of interest include oversedation, respiratory compromise, aspiration, and excessive somnolence. Adverse events will be identified through daily clinical assessment and review of medical records and recorded according to standard ICU reporting practices. This outcome is descriptive and categorical. It is not based on a numerical scale, and minimum or maximum values are not applicable.

Time frame: From the first dose of study medication until ICU discharge, assessed for up to 7 days after randomization, whichever occurs first.

Recruitment Rate

Recruitment rate will be assessed as the proportion of eligible patients who are successfully enrolled and randomized into the study during the recruitment period. The recruitment rate is calculated as the number of randomized participants divided by the total number of eligible patients screened. The recruitment rate ranges from 0% to 100%, with higher values indicating greater feasibility of patient enrollment.

Time frame: During the recruitment period, from first patient screened to last patient randomized.

Medication Adherence to Study Drug

Medication adherence will be assessed as the proportion of prescribed study drug doses that are successfully administered during the intervention period. Adherence will be determined from medication administration records. Medication adherence is expressed as a percentage (%) of planned doses received, ranging from 0% to 100%, where higher values indicate better adherence.

Time frame: Nights 1-3 of the intervention period

Completion Rate of Subjective Sleep Assessments

Completion of subjective sleep assessments will be assessed as the proportion of expected Richards-Campbell Sleep Questionnaire (RCSQ) assessments that are completed by participants. The completion rate ranges from 0% to 100%, with higher values indicating better feasibility of questionnaire-based sleep assessment.

Time frame: Each morning after Nights 1-3 of the intervention period (approximately 08:00).

Adequacy of Actigraphy Wear Time

Adequacy of actigraphy wear time will be assessed using wrist-worn actigraphy (Fitbit Charge 5) and defined as the proportion of nights with valid actigraphy data, according to prespecified criteria for minimum wear duration during the sleep period. Adequacy is expressed as a percentage (%) of monitored nights with valid data, ranging from 0% to 100%, where higher values indicate better feasibility of actigraphy-based sleep monitoring.