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

Suvorexant and Sleep/Delirium in ICU Patients

Sponsors

Lead sponsor: Beth Israel Deaconess Medical Center

Collaborator: Merck Sharp & Dohme Corp.

Source Beth Israel Deaconess Medical Center
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).

Overall Status Active, not recruiting
Start Date February 28, 2020
Completion Date July 1, 2022
Primary Completion Date January 1, 2022
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Nighttime wakefulness after persistent sleep onset (WASO) First night after extubation between 11:00pm and 6:00am
Secondary Outcome
Measure Time Frame
Total sleep time (TST) First night after extubation between 11:00pm and 6:00am
Enrollment 120
Condition
Intervention

Intervention type: Drug

Intervention name: Suvorexant 20 mg

Description: Administration of oral Suvorexant 20 mg

Arm group label: Suvorexant

Other name: Belsomra

Intervention type: Drug

Intervention name: Placebo oral tablet

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

Arm group label: Placebo

Other name: 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.

Gender: All

Minimum age: 60 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Matthias Eikermann, MD, PhD Principal Investigator Beth Israel Deaconess Medical Center
Location
facility Beth Israel Deaconess Medical Center
Location Countries

United States

Verification Date

April 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Suvorexant

Arm group type: Active Comparator

Description: 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.

Arm group label: Placebo

Arm group type: Placebo Comparator

Description: 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.

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

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

Primary purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov