REPOSE Study: Reducing Delirium by Enhancing Postoperative Sleep With Suvorexant

Delirium in Old Age Clinical Trial

— REPOSE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05733286
• Other study ID #: Pro00111869
• Status: Recruiting
• Phase: Phase 2
• Start date: June 28, 2023
• Est. completion date: October 2025

Study information

• Verified date: July 2023
• Source: Duke University
• Contact: Alicja Schultz, MBA
• Phone: 919-681-4377
• Email: alicja.schultz[@]duke.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: October 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Delirium
• Delirium in Old Age

Intervention

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

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Sleep Time	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).	Post operative Day 0-2
Secondary	Postoperative Delirium Severity score	1. 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 or discharge, whichever occurs first.