Suvorexant and Sleep/Delirium in ICU Patients

September 30, 2025 updated by: Balachundhar Subramaniam, Beth Israel Deaconess Medical Center

Effects of the Orexin Receptor Antagonist Suvorexant on Sleep Architecture and Delirium in the Intensive Care Unit: A Multi-Centric Randomized Controlled Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, randomized, placebo-controlled, blinded study. Participants will be enrolled preoperatively. After postoperative extubation, eligible patients will be randomly allocated in a 1:1 ratio to receive either suvorexant 20 mg or placebo.

Study procedures will start on preoperative night 3 when the patient is first asked to report information about their sleep using the Richards-Campbell Sleep Questionnaire (RCSQ). Patients will complete the RCSQ every morning during the 3 days prior to surgery. The intervention (study drug) will be applied for 7 nights starting the night after postoperative extubation in the ICU. Primary and secondary outcomes will be assessed once during the night of the sleep trial in the ICU. The sleep trial will take place during the first night after extubation if the patient has been extubated before 7pm. Exploratory outcomes will be assessed from day of extubation until hospital discharge.

Suvorexant 20 mg or placebo will be administered p.o. once a day between 9:00pm and 10:00pm for a maximum of 7 days starting the night after extubation in the ICU. The study drug will be discontinued after 7 consecutive doses following extubation; or at hospital discharge (if less than 7 days after extubation); or at ICU discharge, if patient showed signs of airway obstruction during sleep or when strong inhibitors of CYP3A are co-administered; or in the event of early termination, subject withdrawal of consent, investigator withdrawal for toxicity or other reasons.

If deemed necessary by the treating clinicians, melatonin or benzodiazepine may be added for treatment of insomnia. All patients will receive usual supportive care as per the treating physicians and standard practice.

Duration of nighttime wakefulness after persistent sleep onset (WASO), total sleep time (TST), time to sleep onset (TSO) will be measured by electroencephalogram (EEG) using a Next Generation SedLine® Brain Function Monitor during the night of the sleep trial. Incidence of postoperative in-hospital delirium and increases delirium free days will be assessed using Confusion Assessment Method (CAM).

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Beth Israel Deaconess Medical Center
    • New York
      • The Bronx, New York, United States, 10467
        • Montefiore Medical Center/Albert Einstein College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  1. Age 60 years or older
  2. 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

Exclusion criteria:

  1. Preoperative left ventricular ejection fraction of less than 30%
  2. Renal failure (creatinine >2 mg/dl or dialysis dependence)
  3. Liver failure (CHILD-Pugh>4)
  4. Coma (RASS<-1)
  5. Signs and symptoms of delirium and agitation at time of enrollment (CAM-ICU positive)
  6. Montreal Cognitive Assessment (MoCA) below 23 at time of consent
  7. 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)
  8. Severe sleep apnea requiring home continuous positive airway pressure treatment
  9. Morbid obesity (BMI >40)
  10. 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).
  11. Patients with known hypersensitivity to study medications
  12. English language limitations (Sleep assessment and delirium assessment tools are only validated in English)
  13. Patients enrolled in other interventional studies which could confound the primary endpoint.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Suvorexant
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
Administration of oral Suvorexant 20 mg
Other Names:
  • Belsomra
Placebo Comparator: Placebo
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
Administration of oral placebo (same non-identifiable form as active comparator)
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nighttime Wakefulness After Persistent Sleep Onset (WASO)
Time Frame: First night after extubation between 11:00pm and 6:00am
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Sleep Time (TST)
Time Frame: First night after extubation between 11:00pm and 6:00am
Total sleep time will be measured by electroencephalogram (EEG) using a Next Generation SedLine® Brain Function Monitor during the night of the sleep trial in analogy to the primary outcome.
First night after extubation between 11:00pm and 6:00am

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Sleep Onset (TSO)
Time Frame: First night after extubation between 11:00pm and 6:00am
Sleep onset latency will be measured by electroencephalogram (EEG) using a Next Generation SedLine® Brain Function Monitor during the night of the sleep trial in analogy to the primary outcome.
First night after extubation between 11:00pm and 6:00am
Duration of Sleep During the Day
Time Frame: Up to 24 hours after initiation of sleep trial
Continuous EEG-monitoring throughout the day following the sleep trial will be performed until no more than 24 hours after initiation of the sleep trial, or until the patient is discharged from the ICU, whichever occurs first. Duration of sleep during the day will be assessed.
Up to 24 hours after initiation of sleep trial
Subjective Sleep Quality: Richards-Campbell Sleep Questionnaire (RCSQ)
Time Frame: Every morning from preoperative day 3 up to postoperative day 7
Subjective sleep quality will be assessed by applying the Richards-Campbell Sleep Questionnaire (RCSQ). The RCSQ is a validated survey instrument for assessing sleep quality in critically ill patients based on a five-item, visual analogue scale (each from 0 [worst value] to 100 [best value]). The scale evaluates perceptions of depth of sleep, sleep onset latency, number of awakenings, time spent awake, and overall sleep quality.
Every morning from preoperative day 3 up to postoperative day 7
Postoperative Delirium
Time Frame: Every day from postoperative day 1 up to day of hospital discharge, an expected average of 21 days
Incidence of postoperative delirium will be measured daily by the Confusion Assessment Method (CAM) and CAM-ICU. The CAM is a standardized screening tool used for identification of delirium symptoms through a diagnostic algorithm based on 4 cardinal features of delirium, namely acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness. The CAM-ICU, which is routinely performed in the ICU, includes both brief cognitive testing and the CAM algorithm to screen for delirium. For CAM-positive patients, the Delirium Symptom Interview, a standard cognitive assessment consisting of tests of attention, orientation, and memory will be performed by a research team members trained in the survey administration methodology and blinded to treatment assignment to verify the CAM screening results.
Every day from postoperative day 1 up to day of hospital discharge, an expected average of 21 days
Delirium-free Days
Time Frame: Every day from postoperative day 1 up to day of hospital discharge, an expected average of 21 days
Incidence of postoperative delirium will be measured daily by the Confusion Assessment Method (CAM) and CAM-ICU. The CAM is a standardized screening tool used for identification of delirium symptoms through a diagnostic algorithm based on 4 cardinal features of delirium, namely acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness. The CAM-ICU, which is routinely performed in the ICU, includes both brief cognitive testing and the CAM algorithm to screen for delirium. For CAM-positive patients, the Delirium Symptom Interview, a standard cognitive assessment consisting of tests of attention, orientation, and memory will be performed by a research team members trained in the survey administration methodology and blinded to treatment assignment to verify the CAM screening results.
Every day from postoperative day 1 up to day of hospital discharge, an expected average of 21 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beth Israel Deaconess Medical Center

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Matthias Eikermann, Montefiore Medical Center/Albert Einstein College of Medicine
  • Principal Investigator: Balachundhar Subramaniam, Beths Israel Deaconess Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 28, 2020

Primary Completion (Actual)

February 26, 2025

Study Completion (Actual)

July 1, 2025

Study Registration Dates

First Submitted

September 13, 2019

First Submitted That Met QC Criteria

September 16, 2019

First Posted (Actual)

September 17, 2019

Study Record Updates

Last Update Posted (Estimated)

October 27, 2025

Last Update Submitted That Met QC Criteria

September 30, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019P000759

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The investigators intend to share de-identified individual participant data that underlie the results reported in the published article following reasonable requests to the principal investigator.

IPD Sharing Time Frame

Data will be made available beginning 9 months and ending 36 months after article publication.

IPD Sharing Access Criteria

Data will be made available to qualified scientific researchers who provide a methodologically sounds proposal following reasonable requests to the principal investigator.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Insomnia

Clinical Trials on Suvorexant 20 mg

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Philippines

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe