Suvorexant and Sleep/Delirium in ICU Patients

NCT ID: NCT04092894

Last Updated: 2025-10-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-28
• Study Completion Date: 2025-07-01

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.

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).

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Suvorexant 20 mg

Intervention Type: DRUG

Administration of oral Suvorexant 20 mg

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.

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

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

Interventions

Suvorexant 20 mg

Administration of oral Suvorexant 20 mg

Intervention Type: DRUG

Placebo oral tablet

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

Intervention Type: DRUG

Other Intervention Names

Belsomra; Placebo

Eligibility Criteria

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.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Balachundhar Subramaniam

Professor of Anesthesia

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Matthias Eikermann

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center/Albert Einstein College of Medicine

Balachundhar Subramaniam

Role: PRINCIPAL_INVESTIGATOR

Beths Israel Deaconess Medical Center

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Montefiore Medical Center/Albert Einstein college of Medicine

The Bronx, New York, United States

Countries

United States

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2019P000759

Identifier Type: -

Identifier Source: org_study_id