REPOSE Study: Reducing Delirium by Enhancing Postoperative Sleep With Suvorexant (REPOSE)

Efficacy of Suvorexant to Improve Postoperative Sleep and Reduce Delirium Severity in Older Surgical Patients: A Double-blinded, Randomized, Placebo-controlled Trial

This research study will evaluate the effectiveness of postoperative administration of a drug called suvorexant, to improve postoperative sleep and decrease the severity of delirium (serious confusion) in adults 65 years and older undergoing non-cardiac surgery.

Study Overview

• Status: Completed
• Conditions: Delirium in Old Age
• Intervention / Treatment: Drug: Suvorexant 20 mg; Drug: Placebo

Detailed Description

Suvorexant is an FDA-approved drug to treat a condition called insomnia, a sleep disorder characterized by difficulty falling asleep, staying asleep or getting good quality sleep, and has been found to have a good safety profile in older adults. Since older surgical patients often have difficulties with sleep, suvorexant might improve sleep after surgery but this remains unknown. Because difficulties with sleeping after surgery have been associated with a disorder of severe confusion called delirium, administration of suvorexant after surgery may also help prevent delirium or decrease its severity.

Participants will receive either a placebo or suvorexant by mouth (or feeding tube if present) on the first three nights after surgery while in the hospital. Prior to surgery, participants will be asked to wear a wristband sleep monitor and complete several questionnaires about their sleep, brief thinking and memory tests, a test of attention, and a measurement of their pupil size with a special camera. After surgery, participants will wear a comfortable headband device that records the electrical signals from the brain to measure the amount and depth of their sleep. This device will be worn for the first 3 nights from 9:00 PM to 6:00 AM after surgery or until hospital discharge, whichever occurs first. After surgery, participants will also answer several questions about their sleep quality and redo some of the brief thinking and memory tests (delirium tests), attention tests, and pupil size measurements. Additionally, the investigators will collect a blood sample prior to surgery and on the first two days after surgery.

Benefits of this study include the possibility of improved sleep after surgery and fewer problems with confusion and thinking and memory problems after surgery.

Risks of participation include headache, diarrhea, dry mouth, cough, abnormal dreams, dizziness, daytime tiredness and discomfort from the blood draw.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age 65 and older
2. Undergoing non-cardiac, non-intracranial surgery, any surgical procedure not involving the skull, brain, cerebrovascular structures
3. Scheduled postoperative inpatient overnight stay
4. Able to give informed consent or has legally authorized representative able to give informed consent on their behalf
5. English-speaking

Exclusion Criteria:

1. Inmate of correctional facility
2. Body mass index> 40
3. Legal blindness
4. Unable to perform study related questionnaires and assessments
5. Use of outpatient sedating sleep aids > 2 times per any week in 1 month preceding day of surgery. Sedating sleep aids, *See list Below.
6. History of psychotic disorder, including schizophrenia, schizoaffective disorder, schizophreniform or brief psychotic disorder.
7. History of liver failure with documented international normalized ratio (INR) of >1.2 or with history of hepatic encephalopathy
8. History of severe sleep apnea or obesity hypoventilation syndrome requiring home bilevel positive airway pressure therapy or home ventilator or other forms of noninvasive ventilation
9. Chronic lung disease requiring home oxygen therapy
10. History of narcolepsy
11. Use of systemic (oral, intravenous, intramuscular, subcutaneous) moderate or strong CYP3A inhibitors within 1 week prior to surgery, *See list below
12. Use of systemic (oral, intravenous, intramuscular, subcutaneous) moderate or strong CYP3A inducers within 1 week prior to surgery, *See list below.
13. Current or planned administration of digoxin, or is currently experiencing digoxin toxicity
14. Undergoing surgery that will result in inability to take medications by mouth including laryngectomy, tracheostomy, and oral resection/reconstructive surgery
15. Undergoing surgery that will require postoperative strict bowel rest, including gastrectomy, esophagectomy, and pancreaticoduodenectomy
16. Undergoing surgery in an area that will make it unsafe to wear a headband, such as scalp or forehead procedures.
17. Inappropriate for study inclusion based on the judgement of the principal investigator

Exclusionary Medications:

Moderate CYP3A inhibitors: Amprenavir, Aprepitant, Atazanavir, Ciprofloxacin, Diltiazem, Erythromycin, Fluconazole, Fosamprenavir, Imatinib, Verapamil, grapefruit juice.

Strong CYP3A inhibitors: Ketoconazole, Itraconazole, Posaconazole, Clarithromycin, Nefazodone, Ritonavir, Saquinavir, Nelfinavir, Indinavir, Boceprevir, Telaprevir, Telithromycin, Conivaptan

Moderate/Strong CYP3A inducers: Apalutamide, Carbamazepine, Enzalutamide, Ivosidenib, lumacaftor, Mitotane, Phenytoin, Rifampin, St. John's wort, Bosentan, Cenobamate, Dabrafenib, Efavirenz, Etravirine, Lorlatinib, Pexidartinib, Phenobarbital, Primidone, Sotorasib.

Sedating sleep aids: Mirtazapine, Trazodone, Flurazepam, Temazepam, Triazolam, Estazolam, Quazepam, Clonazepam, Lorazepam, Midazolam, Alprazolam, Diazepam, Zolpidem, Zaleplon, Eszopiclone, Diphenhydramine, Doxylamine, Hydroxyzine, Suvorexant, Doxepin

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
Placebo Comparator: Placebo Arm	Drug: Placebo; Administer Suvorexant versus placebo every evening for Post-Operative Day (POD) 0,1, &2
Active Comparator: Suvorexant Arm	Drug: Suvorexant 20 mg; Administer Suvorexant versus placebo every evening for Post-Operative Day (POD) 0,1, &2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Sleep Time (TST) on the First Postoperative Night	Total sleep time (TST) on first postoperative night that patient received study drug, as measured by electroencephalography (EEG). Total sleep time includes amount of time in sleep during the lights out period (defined between 21:00 and 06:00).	The first postoperative night that the participants received study drug (D0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Postoperative Delirium Severity Score	Three minute Confusion Assessment Method (3D-CAM ) severity scores up through postoperative day 5 or discharge, whichever occurs first, in patients receiving suvorexant vs placebo. Scores range from 0-20 and the higher score is worse.	Postoperative Day 0 through Day 5

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Average Electrographic Total Sleep Time Over the 3-night Recording Period	Using the electrographic headband data, differences in postoperative sleep architecture (including stage 2 and 3 NREM sleep and REM sleep) will be compared in participants who received suvorexant compared to those who received placebo using two-sample t-tests. No multiple comparison correction for multiple sleep stages is planned because these are exploratory analyses. Average total sleep time over all nights that participants receive study drug will also be compared using two-sample t-tests.	Postoperative day 0-2
Average Postoperative Richards-Campbell Subjective Sleep Quality Scores	To assess subjective sleep quality, the Richards-Campbell subjective sleep quality questionnaire will be administered daily from postoperative day 1-5 or until hospital discharge, whichever occurs first. The total subjective sleep quality score will be compared between placebo and suvorexant groups using a two-sample t-test.	Postoperative days 1-5
Change In Pupil Diameter Fluctuations From Preoperative Baseline Through Postoperative Day 3	Pupillary unrest under ambient light is an index of spontaneous pupil fluctuations that occur secondary to activity of the locus coeruleus, an important brainstem nucleus involved in maintenance of wakefulness and attentional control. Decreased wakefulness has been associated with decreased pupillary unrest at ambient light, suggesting that pupillary unrest at ambient light is a marker of sleep deprivation-related alterations in wakefulness and attention. Here, infrared pupillometry will be used to measure participant's pupil diameter fluctuations under ambient light conditions both before surgery and daily up through postoperative day 3. We will compare postoperative changes in pupillary unrest at ambient light in both suvorexant and placebo-treated using a two-sided t-test.	Preoperative baseline and postoperative days 1-3
Changes in Average Response Latency on Preoperative and Postoperative Psychomotor Vigilance Testing	Sleep deprivation results in decreased ability to sustain attention, which can be measured with the 5-minute psychomotor vigilance task. The psychomotor vigilance task measures simple reaction times to a visual stimulus over a minute to assess for slowed responses and lapses (i.e., failed response to visual stimuli). Response times, speed, and lapses will be compared between suvorexant and placebo-treated groups to see if postoperative nightly suvorexant has an effect on these sustained attention measures. Using the NASA PVT+ application on an Apple iPad, the psychomotor vigilance task will be collected before surgery, and daily on postoperative day 1-3, or until hospital discharge, whichever occurs first. Analyses will examine pre-to-postoperative change in sustained attention measures to adjust for preoperative performance variability between participants.	Preoperative baseline, and postoperative days 1-3
Postoperative Hospital Length of Stay	Postoperative delirium occurs in up to 40% of older surgical patients and has been associated with prolonged hospital stays, long-term cognitive impairment, and increased one-year postoperative mortality. We will record the length of hospital stay for each participant.	From Postoperative day 0 up to 4 week follow up visit

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Michael Devinney Jr, MD, PhD, Duke University

Publications and helpful links

General Publications

• Fallon JM, Hashemaghaie M, Peterson CE, Tran D, Wu SR, Valdes JM, Pedicini NM, Adams ME, Soltis M, Mansour W, Wright MC, Raghunathan K, Treggiari MM, Sasannejad C, Devinney MJ. Protocol and design of the REPOSE study: a double-blinded, randomised, placebo-controlled trial to evaluate the efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older patients undergoing non-cardiac surgery. BMJ Open. 2025 Mar 13;15(3):e091099. doi: 10.1136/bmjopen-2024-091099.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2023
• Primary Completion (Actual): June 25, 2025
• Study Completion (Actual): July 7, 2025

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: February 8, 2023
• First Posted (Actual): February 17, 2023

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: December 24, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Sleep
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Neurotransmitter Agents; Hypnotics and Sedatives; suvorexant
• Other Study ID Numbers: Pro00111869

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: No