Clinical trial NCT04092894: Suvorexant and Sleep/Delirium in ICU Patients
Official title: Effects of the Orexin Receptor Antagonist Suvorexant on Sleep Architecture and Delirium in the Intensive Care Unit: A Multi-Centric Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Insomnia
Sleep Fragmentation
Sleep Initiation and Maintenance Disorders
Postoperative Delirium
Keywords: Suvorexant
Sleep architecture
Delirium
Intensive care unit
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2019-09-17
Enrollment: 120
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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).

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.

Primary outcomes:
measure: Nighttime wakefulness after persistent sleep onset (WASO)
timeFrame: First night after extubation between 11:00pm and 6:00am
Secondary outcomes:
measure: Total sleep time (TST)
timeFrame: First night after extubation between 11:00pm and 6:00am
Other outcomes:
measure: Time to sleep onset (TSO)
timeFrame: First night after extubation between 11:00pm and 6:00am
measure: Duration of sleep during the day
timeFrame: Up to 24 hours after initiation of sleep trial
measure: Subjective sleep quality: Richards-Campbell Sleep Questionnaire (RCSQ)
timeFrame: Every morning from preoperative day 3 up to postoperative day 7
measure: Postoperative delirium
timeFrame: Every day from postoperative day 1 up to day of hospital discharge, an expected average of 21 days
measure: Delirium-free days
timeFrame: Every day from postoperative day 1 up to day of hospital discharge, an expected average of 21 days
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Bronx
country: United States
facility: Montefiore Medical Center/Albert Einstein college of Medicine
state: New York
Study officials:
affiliation: Montefiore Medical Center/Albert Einstein College of Medicine
name: Matthias Eikermann
role: PRINCIPAL_INVESTIGATOR
affiliation: Beths Israel Deaconess Medical Center
name: Balachundhar Subramaniam
role: PRINCIPAL_INVESTIGATOR
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