Efficacy of Suvorexant on Post-operative Sleep Disturbance

Improvement of Restorative Sleep and Post-surgical Insomnia Following Suvorexant Administration

The study is a parallel group, double blind, randomized trial. Subjects will be recruited from individuals undergoing elective surgery for orthopedic, abdominal, urologic, gynecologic or spine reasons. Out of 92 subjects, one experimental group of 46 subjects will receive 20 mg Suvorexant beginning the first in-hospital night ("day 0") and continuing for their hospital stay. If the dose is not well tolerated (e.g., daytime sleepiness), then the dose may be decreased to 10 mg of Suvorexant.

For blinding purposes each arm will receive two tablets (two 10 mg tablets or one 10 mg tablet and a placebo). The other control group of 46 subjects will receive placebo (two tablets) and treatment as usual.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Delirium; Postoperative Insomnia
• Intervention / Treatment: Drug: Suvorexant; Drug: Placebo

Detailed Description

It is rare to get a good night's sleep in the hospital. Even routine patient care, including alarm systems, and too much light can lead to sleep disturbance. Failure to achieve enough high-quality sleep has been associated with decreased brain and heart function. The investigators aim to restore usual sleep patterns in hospitalized patients to have a positive influence on patient outcomes and healthcare costs. Suvorexant, the tested drug in our protocol, works on a different brain chemical system than most other sleep drugs, which may account for its ability to restore natural sleep. Suvorexant has been shown to reduce wakefulness during sleep by a reduction in long wake bouts. This reduction has a positive effect on sleep quality. In keeping with Suvorexant's established ability to decrease insomnia in outpatient settings, the investigators will assess its efficacy to improve sleep quality in the hospital environment in patients having surgery who have sleep disturbance. Suvorexant will be administered beginning on the night after surgery and through the hospitalization (it is estimated that stays will be 1-3 days; the investigators will set a maximum of 5 days). If the dose is not well tolerated (e.g., daytime sleepiness), then the dose may be decreased to 10 mg of Suvorexant. The investigators aim to study the participant's sleep patterns by using a self-wearable electroencephalography (EEG) recording device, the Sleep Profiler, and see patterns such as total sleep time or the stages of sleep such as rapid eye movement (REM), non-REM, etc. Additionally, the investigators hope to determine if concentration, attention, and general cognitive performance are improved as a result of better sleep. Promoting "natural sleep" may improve surgical recovery through the lessening of fatigue and improvements in brain health.

• Study Type: Interventional
• Enrollment (Anticipated): 92
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Paul S. Garcia, MD PhD; Phone Number: 212-304-7523; Email: pg2618@cumc.columbia.edu
• Study Contact Backup: Name: Meah T. Ahmed, BSBme; Email: ma4373@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center/NewYork-Presbyterian Milstein Hospital/New York State Psychiatric Institute
      • Contact: Paul S. Garcia, MD PhD; Phone Number: 212-304-7523; Email: pg2618@cumc.columbia.edu
      • Contact: Meah T. Ahmed, BSBme; Email: ma4373@cumc.columbia.edu
      • Sub-Investigator: Terry E. Goldberg, PhD
      • Principal Investigator: Paul S. Garcia, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Aged 50 years to 90 years old.
• Patients getting elective surgeries for orthopedic reasons (e.g., hip or knee replacement), abdominal surgery (e.g., hernia repair, renal cancer), urologic or gynecologic surgery, and spine surgery with a projected inpatient stay of 24 hours or longer.
• Patients experiencing insomnia characterized by difficulties with sleep onset, early morning awakening, and/or sleep maintenance three or more times weekly over a three-month period for eligibility.

Exclusion criteria:

• Patients who undergo surgery and then are admitted to intensive care.
• Coronary artery bypass graft (CABG) or other cardiac surgeries.
• Intra-cranial surgery.
• Chronic pain (i.e., patients on opioid medications as an outpatient).
• Circadian rhythm disorders.
• High Beck Depression or Beck Anxiety scores.
• Moderate to severe dementia (failed 3D CAM)
• Severe obstructive sleep apnea (OSA) (Apnea-hypopnea index (AHI)>30 and/or screen high risk)
• Patients receiving Cytochrome P-450 (CYP3) inhibitors or inducers (Inhibitors: clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal, and grapefruit. Inducers: phenobarbital, phenytoin, rifampicin, St. John's Wort, and glucocorticoids).
• Vulnerable populations (i.e., children, pregnant women, non-English speaking patients).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Suvorexant administration; Subjects will receive 20 mg Suvorexant beginning the first in-hospital night ("day 0") and continuing for their hospital stay. If the dose is not well tolerated (e.g., daytime sleepiness), then the dose may be decreased to 10 mg of Suvorexant. For blinding purposes, each arm will receive two tablets (two 10 mg tablets or one 10 mg tablet and a placebo). Suvorexant will be administered beginning on the night after surgery and through the hospitalization period (it is estimated that stays will be 1-3 days; subjects will be followed for a maximum of 5 days).	Drug: Suvorexant; Suvorexant (Belsomra™) is an orexin receptor antagonist that will be administered as 2 tablets (10mg each) for a starting dose of 20mg. If the dose is not well tolerated (e.g., daytime sleepiness), then the dose may be decreased to 10 mg of Suvorexant.; Other Names: Belsomra
Placebo Comparator: Placebo administration; Subjects will receive a placebo (two tablets) and treatment as usual. The placebo will be administered beginning on the night after surgery and through the hospitalization period (it is estimated that stays will be 1-3 days; subjects will be followed for a maximum of 5 days).	Drug: Placebo; The placebo pill will look identical to Suvorexant and will be taken as 2 tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total sleep time on day 0 (TST)	Analysis will be adjusted for group baseline differences, including pre-existing cognitive impairment, medical co-morbidities, and the type and duration of surgery.	Day 0 of in-hospital stay after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal trend of TST	The longitudinal trend of TST over the five days will be measured using mixed-effect regression. Group, time (day 0-4), and group x time will be included as the fixed effects and a random intercept of subjects to account for within-subject correlation due to repeated measurement. Regression quotients will be reported.	Up to Day 5 post-surgery
Rate of attrition	The rate of attrition over the 5 days will be measured. If any specific patterns are identified, inverse propensity treatment weighting will be performed to adjust the effect of nonrandom dropout.	Up to Day 5 post-surgery
Richards Campbell Self-Report Sleep Scale	The Richards Campbell self-report sleep scale will be used to determine the quality of sleep each morning. This five-item, visual analogue scale was designed as an outcome measure for assessing the perception of sleep. The scale evaluates perceptions of depth of sleep, sleep onset latency, number of awakenings, time spent awake, and overall sleep quality. For each item, respondents are given a visual analogue scale and are asked to place a mark on the line indicating where their own experiences fit between two extremes (for example, the degree to which they received a "good night's sleep" or "a bad night's sleep"). Scale lines extend from 0 to 100 mm, and scores are calculated by measuring where responses fall on each line. A total score is obtained by summing each score out of 100 and dividing the total by five. Lower scores indicate a poorer quality of sleep (worse outcome).	Up to Day 5 post-surgery
Incidence of Delirium	The 3-minute diagnostic interview for Confusion Assessment Method (CAM)-defined delirium (3D-CAM) is a brief verbal assessment tool that can be used to test for delirium. For all items, if the subject's answer is 'incorrect', 'yes', 'don't know', 'no response', or 'non-sensical response', then the appropriate (unshaded) column on the right side is checked. Each of the 4 columns designates a CAM feature. If any one box in a column is checked, the feature is considered present. The CAM algorithm is considered positive if the following features are present: Feature 1) Acute onset or fluctuating course and Feature 2) Inattention and either Feature 3) Disorganized thinking or Feature 4) Altered level of consciousness.	Up to Day 5 post-surgery

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Paul S. Garcia, MD PhD, Columbia University

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): May 1, 2025
• Study Completion (Anticipated): May 1, 2025

Study Registration Dates

• First Submitted: April 10, 2023
• First Submitted That Met QC Criteria: April 10, 2023
• First Posted (Actual): April 21, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Insomnia; Sleep quality; Sleep Disturbance; Suvorexant
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Suvorexant
• Other Study ID Numbers: AAAU4343

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be shared in aggregate form. There is no plan to share individual participant data (IPD) with researchers not involved with the study design. Several posthoc analyses are being planned for retrospective analysis of the data obtained.

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