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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Suvorexant Arm | Active Comparator |
| |
| Placebo Arm | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Suvorexant 20 mg | Drug | Administer Suvorexant versus placebo every evening for Post-Operative Day (POD) 0,1, &2 |
|
| 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) |
| 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 |
| 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. |
Inclusion Criteria:
Exclusion Criteria:
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
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| Name | Affiliation | Role |
|---|---|---|
| Michael Devinney Jr, MD, PhD | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40081971 | Derived | 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. |
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14 participants were never assigned to a treatment arm due to screen fail (n= 4), withdrawal by PI (n = 4), subject chose to withdraw prior to surgery (n = 3), and surgery cancellation (n =3).
Patients age 65 or older scheduled for non-cardiac elective surgery with planned postoperative overnight stay at Duke University Hospital and Duke Medical Pavilion were contacted to determine interest in enrollment in this study. Patients were consented in-person at preoperative visits or via electronic consent over telephone or videoconferencing.
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| ID | Title | Description |
|---|---|---|
| FG000 | Suvorexant Arm | Administer Suvorexant every evening for Post-Operative Day (POD) 0, 1, and 2 |
| FG001 | Placebo Arm | Administer placebo every evening for Post-Operative Day (POD) 0, 1, and 2 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants who received a dose of study drug or placebo.
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| ID | Title | Description |
|---|---|---|
| BG000 | Suvorexant Arm | Administer Suvorexant every evening for Post-Operative Day (POD) 0, 1, and 2 |
| BG001 | Placebo Arm | Administer placebo every evening for Post-Operative Day (POD) 0, 1, and 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Participants with EEG data for total sleep time determination. | Posted | Mean | Standard Deviation | hours | The first postoperative night that the participants received study drug (D0) |
|
Surgery (day 0) to 4-week follow-up call
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Suvorexant Arm | Administer Suvorexant every evening for Post-Operative Day (POD) 0, 1, and 2 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial Fibrillation | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leg Spasms | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Devinney, MD, PhD | Duke University | 919-668-6266 | michael.devinney@duke.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 21, 2022 | Dec 22, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| C551624 | suvorexant |
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Dosing labels will be attached to each study drug dose and include pre-printed fields with
| Placebo | Drug | Administer Suvorexant versus placebo every evening for Post-Operative Day (POD) 0,1, &2 |
|
| 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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
|
|
| Secondary | 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. | Participants with 3D-CAM delirium severity scores collected. | Posted | Median | Inter-Quartile Range | score on a scale | Postoperative Day 0 through Day 5 |
|
|
|
|
| Other Pre-specified | 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. | Not Posted | Postoperative day 0-2 | Participants |
| Other Pre-specified | 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. | Not Posted | Postoperative days 1-5 | Participants |
| Other Pre-specified | 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. | Not Posted | Preoperative baseline and postoperative days 1-3 | Participants |
| Other Pre-specified | 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. | Not Posted | Preoperative baseline, and postoperative days 1-3 | Participants |
| Other Pre-specified | 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. | Not Posted | From Postoperative day 0 up to 4 week follow up visit | Participants |
| 1 |
| 66 |
| 9 |
| 66 |
| 14 |
| 66 |
| EG001 | Placebo Arm | Administer placebo every evening for Post-Operative Day (POD) 0, 1, and 2 | 0 | 57 | 9 | 57 | 13 | 57 |
| Cardiac Arrest | Cardiac disorders | Systematic Assessment |
|
| Intraoperative cardiac arrest | Cardiac disorders | Systematic Assessment |
|
| Paroxysmal Atrial Tachycardia | Cardiac disorders | Systematic Assessment |
|
| Erythematous rash | Infections and infestations | Systematic Assessment |
|
| Postoperative Spinal Abscess | Infections and infestations | Systematic Assessment |
|
| Postoperative Seroma Infection | Infections and infestations | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| Wound dehiscence | Infections and infestations | Systematic Assessment |
|
| Wound Infection | Infections and infestations | Systematic Assessment |
|
| Abdominal Fluid Collection | Injury, poisoning and procedural complications | Systematic Assessment |
|
| acute blood loss anemia from intraoperative aortic injury | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Increased Postoperative Pain | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Surgical Incision Swelling | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Gout | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Death due to persistent comatose state | Nervous system disorders | Systematic Assessment |
|
| Intraparenchymal hemorrhage | Nervous system disorders | Systematic Assessment |
|
| Multifocal Acute Brain Infarcts | Nervous system disorders | Systematic Assessment |
|
| Transient Ischemic Attack | Nervous system disorders | Systematic Assessment |
|
| Acute Kidney Injury | Renal and urinary disorders | Systematic Assessment |
|
| Postoperative Urinoma | Renal and urinary disorders | Systematic Assessment |
|
| Urinary Incontinence | Renal and urinary disorders | Systematic Assessment |
|
| Aspiration pneumonitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hemorrhagic Shock | Vascular disorders | Systematic Assessment |
|
| Hypotension | Vascular disorders | Systematic Assessment |
|
| Pulmonary embolism | Vascular disorders | Systematic Assessment |
|
| Pulmonary Embolus | Vascular disorders | Systematic Assessment |
|
| Self-reported somnolence | Nervous system disorders | Systematic Assessment |
|
| Observed somnolence | Nervous system disorders | Systematic Assessment |
|
| Abnormal Dreams | Psychiatric disorders | Systematic Assessment |
|
| Hypnagogic Hallucinations | Psychiatric disorders | Systematic Assessment |
|
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