Suvorexant and Sleep/Delirium in ICU Patients

Phase 4

Recruiting

• Conditions: Insomnia; Sleep Fragmentation; Postoperative Delirium; Sleep Initiation and Maintenance Disorders
• Interventions: Drug: Suvorexant 20 mg; Drug: Placebo oral tablet

• Registration Number: NCT04092894
• Lead Sponsor: 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).

Study Timeline

• Study First Submitted: 2019-09-13
• Study First Submitted QC: 2019-09-16
• Study First Posted: 2019-09-17
• Study Start: 2020-02-28
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-15
• Last Update Posted: 2023-11-18
• Primary Completion: 2024-12-31
• Study Completion: 2025-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Suvorexant	Suvorexant 20 mg	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.
Placebo	Placebo oral tablet	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.

Primary Outcome Measures

Name	Time	Method
Nighttime wakefulness after persistent sleep onset (WASO)	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.

Secondary Outcome Measures

Name	Time	Method
Total sleep time (TST)	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.

Trial Locations

Locations (2)

Montefiore Medical Center/Albert Einstein college of Medicine; 🇺🇸 Bronx, New York, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States