Suvorexant and Sleep/Delirium in ICU Patients

NCT04092894 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2019P000759
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

Investigators will evaluate the efficacy of postoperative oral suvorexant treatment on nighttime wakefulness after persistent sleep onset (WASO) among adult cardiac surgical patients recovering in the cardiac intensive care unit (ICU). The study include patients ≥ 60 years old undergoing coronary artery bypass graft surgery (CABG), with or without valve surgery (aortic or mitral). Patients will receive either oral suvorexant or placebo for 7 nights starting the night after extubation. The primary hypothesis is that suvorexant compared with placebo decreases WASO, as measured by a specialized electroencephalogram (EEG), the SedLine monitor, during the first night in the cardiac ICU. Investigators will also assess total sleep time (TST), time to sleep onset (TSO), and postoperative delirium and delirium-free days.

Conditions

Insomnia; Sleep Fragmentation; Sleep Initiation and Maintenance Disorders; Postoperative Delirium

Keywords

Suvorexant; Sleep architecture; Delirium; Intensive care unit

Outcome Measures

Primary Outcomes (1)

• Nighttime Wakefulness After Persistent Sleep Onset (WASO)

  Nighttime wakefulness after persistent sleep onset (WASO) will be measured using a SedLine® Brain Function Monitor. WASO will be defined as the duration of wakefulness after the onset of persistent sleep in the observation period between 11:00pm (Lights-Off) to 6:00am (Lights-On) in minutes. Onset of persistent sleep will be defined as the first epoch of 10 consecutive minutes of sleep (REM or non-REM Stages 1, 2, 3 or 4) after Lights-Off. Wakefulness will be defined as any epoch of Stage 0. Sleep staging will be performed according to Rechtschaffen \& Kales criteria and in accordance with AASM guidelines. The SedLine® monitor uses a symmetrical bilateral array of sensors that provides four-channel data.

  First night after extubation between 11:00pm and 6:00am

Secondary Outcomes (1)

• Total Sleep Time (TST)

  First night after extubation between 11:00pm and 6:00am

Other Outcomes (5)

• Time to Sleep Onset (TSO)

  First night after extubation between 11:00pm and 6:00am

• Duration of Sleep During the Day

  Up to 24 hours after initiation of sleep trial

• Subjective Sleep Quality: Richards-Campbell Sleep Questionnaire (RCSQ)

  Every morning from preoperative day 3 up to postoperative day 7

Study Arms (2)

Suvorexant

ACTIVE COMPARATOR

Suvorexant 20 mg will be administered p.o. once a day between 9:00pm and 10:00pm for 7 days starting the night after extubation in the ICU.

Drug: Suvorexant 20 mg

Placebo

PLACEBO COMPARATOR

Placebo will be administered p.o. once a day between 9:00pm and 10:00pm for 7 days starting the night after extubation in the ICU.

Drug: Placebo oral tablet

Interventions

Suvorexant 20 mg DRUG

Administration of oral Suvorexant 20 mg

Also known as: Belsomra

Suvorexant

Placebo oral tablet DRUG

Administration of oral placebo (same non-identifiable form as active comparator)

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 60 years or older
• Undergoing elective coronary artery bypass graft surgery with or without aortic and/or mitral valve replacement, who are expected to be transferred to the ICU postoperatively

You may not qualify if:

• Preoperative left ventricular ejection fraction of less than 30%
• Renal failure (creatinine \>2 mg/dl or dialysis dependence)
• Liver failure (CHILD-Pugh\>4)
• Coma (RASS\<-1)
• Signs and symptoms of delirium and agitation at time of enrollment (CAM-ICU positive)
• Montreal Cognitive Assessment (MoCA) below 23 at time of consent
• Psychiatric or neurologic diseases (including chronic benzodiazepine use, bipolar disorder, psychotic disorder, posttraumatic stress disorder, requirement of prophylactic psychiatric medication, evidence of acute depression on screening visit, preexisting cognitive impairment, Alzheimer disease, Parkinson's disease, medications for cognitive decline, history of recent seizures (within 1 year prior visit), alcoholism or documented history of alcohol abuse, and narcolepsy)
• Severe sleep apnea requiring home continuous positive airway pressure treatment
• Morbid obesity (BMI \>40)
• Known or suspected pregnancy (there are no adequate and well-controlled studies of suvorexant in pregnant women. Based on animal data, Suvorexant may cause fetal harm).
• Patients with known hypersensitivity to study medications
• English language limitations (Sleep assessment and delirium assessment tools are only validated in English)
• Patients enrolled in other interventional studies which could confound the primary endpoint.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Montefiore Medical Center/Albert Einstein college of Medicine

The Bronx, New York, 10467, United States

Location

Related Publications (18)

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• Azimaraghi O, Hammer M, Santer P, Platzbecker K, Althoff FC, Patrocinio M, Grabitz SD, Wongtangman K, Rumyantsev S, Xu X, Schaefer MS, Fuller PM, Subramaniam B, Eikermann M. Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit. BMJ Open. 2020 Jul 19;10(7):e038474. doi: 10.1136/bmjopen-2020-038474.

  PMID: 32690536 DERIVED

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Sleep Deprivation; Emergence Delirium; Delirium

Interventions

suvorexant

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Confusion; Neurobehavioral Manifestations; Postoperative Complications; Pathologic Processes; Neurocognitive Disorders

Limitations and Caveats

Metabolic and biochemical derangements in critically ill patients impact drug pharmacokinetics and pharmacodynamics, complicating dose optimization; under the conditions studied, this may have led to an inadequate dose being administered in our study

Results Point of Contact

• Title: Balachundhar Subramaniam
• Organization: Beth Israel Deaconess Medical Center

bsubrama@bidmc.harvard.edu

7814750572

Study Officials

• Matthias Eikermann

  Montefiore Medical Center/Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

• Balachundhar Subramaniam

  Beths Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesia

Model Details: Randomization in a 1:1 ratio (suvorexant 20 mg versus placebo) will be stratified by duration of perioperative anesthesia and sedation.

Study Record Dates

• First Submitted: September 13, 2019
• First Posted: September 17, 2019
• Study Start: February 28, 2020
• Primary Completion: February 26, 2025
• Study Completion: July 1, 2025
• Last Updated: October 27, 2025
• Results First Posted: October 27, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available beginning 9 months and ending 36 months after article publication.
• Access Criteria: Data will be made available to qualified scientific researchers who provide a methodologically sounds proposal following reasonable requests to the principal investigator.

Locations

US (2)