reALIGNing Circadian Rhythm and Promoting Sleep in the Intensive Care Unit

ALIGN-ICU is a prospective, multicentre, parallel-group pilot randomized controlled trial evaluating the implementation of a multifaceted sleep chronobundle within routine critical care workflows. The intervention combines circadian entrainment strategies with overnight sleep promotion to address both daytime and nighttime contributors to sleep and circadian disruption.

Critical illness can disrupt circadian physiology through abnormal light exposure, irregular feeding and activity patterns, sedative administration, and frequent nighttime care interruptions. Existing sleep-promotion approaches predominantly address the nighttime environment. ALIGN-ICU integrates daytime environmental and behavioural cues with nighttime sleep protection, with the rationale that coordinated delivery may better support circadian alignment than individual components alone.

The chronobundle comprises bright light exposure at 10,000 lux from 09:00 to 13:00; scheduled enteral feeding at 08:00, 12:00, 16:00, and 20:00; one daily mobility or exercise session between 09:00 and 15:59; and overnight sleep promotion from 22:00 to 06:00, including a protected sleep period from 00:00 to 04:00. Non-urgent care activities will be rescheduled when clinically appropriate. Intervention delivery will accommodate patient-specific clinical needs, with modifications, withheld components, and reasons for deviations documented. Treatment will continue on the ward to complete seven days when ICU discharge occurs earlier.

Allocation will be performed through a centralized REDCap randomization system using variable block sizes. Because the intervention involves visible changes to bedside care, implementation will emphasize standardized delivery across participating centres. Sites will receive training, implementation manuals, bedside checklists, and quick-reference materials. Local clinical champions and designated research coordinators will support delivery, troubleshoot barriers, and reinforce adherence. Prospective documentation, regular audits, and feedback to sites will inform assessment of intervention fidelity and opportunities for refinement.

The pilot will characterize recruitment processes, delivery within competing clinical workflows, and participant and clinician adherence. Participant feedback near hospital discharge will explore the acceptability, appropriateness, and duration of individual intervention components and study procedures. Portable polysomnography and physiological circadian measures will provide complementary information about sleep and biological responses.

Analyses will be primarily descriptive. Clinical and biological estimates will be reported with measures of uncertainty; no formal efficacy hypothesis testing is planned. Findings will guide intervention refinement, implementation procedures, and the design of a subsequent adequately powered multicentre efficacy trial.

• Sleep chronobundle (Combination product), also known as Bright light therapy, Scheduled intermittent feeding, Daily mobility, Overnight sleep promotion: Participants in the intervention arm will receive usual ICU care plus a multifaceted sleep chronobundle comprising: 1. Bright light therapy at 10,000 lux daily from 09:00 to 13:00. 2. Scheduled enteral feeding at 08:00, 12:00, 16:00, and 20:00. 3. One daily mobility or exercise session between 09:00 and 15:59, adapted to clinical condition. 4. Overnight sleep promotion from 22:00 to 06:00, including protected sleep from 00:00 to 04:00, with non-urgent care rescheduled when clinically appropriate. The intervention will be delivered for seven days, extending to up to 10 days at investigator discretion. If ICU discharge occurs before day seven, it will continue on the ward to complete seven days. Components may be modified or withheld for clinical reasons, with deviations and their rationale documented.
• Control (Other): Participants in the control arm will receive usual ICU care according to local clinical practices, including routine management of nutrition, mobility, sleep, sedation, and delirium. Study personnel will not provide prompts to implement the sleep chronobundle. Clinically indicated care will remain at the discretion of the treating team. Control participants will undergo the same study assessments and follow-up as those in the intervention arm.

Primary outcomes

• Recruitment rate [2 years]: The primary outcome is feasibility of conducting the trial and implementing the sleep chronobundle, assessed by recruitment rate, consent rate, time from eligibility to randomization, and protocol adherence. Feasibility targets are recruitment of at least one participant per site per month, consent from more than 50% of eligible participants approached, and adherence to at least 75% of prescribed intervention components. Delivery of each component and reasons for missed or modified delivery will be documented prospectively.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age 18 years or older.
* Admission to a participating ICU.
* Expected ICU stay of at least 48 hours.
* Respiratory failure requiring invasive mechanical ventilation, non-invasive ventilation, or high-flow oxygen therapy, or shock requiring vasopressor therapy.
* Receipt of intermittent or continuous sedation.

Exclusion Criteria:

* Comfort-focused care or anticipated death.
* Severe chronic neurologic disability.
* Acute brain injury.
* Known circadian rhythm disorder.
* Blindness or optic nerve disease.
* Contraindication to the daytime feeding schedule.
* Acute drug overdose.
* Active alcohol withdrawal syndrome.