Clinical trial NCT05733286: REPOSE Study: Reducing Delirium by Enhancing Postoperative Sleep With Suvorexant
Official title: Efficacy of Suvorexant to Improve Postoperative Sleep and Reduce Delirium Severity in Older Surgical Patients: A Double-blinded, Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Delirium in Old Age
Keywords: Sleep
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2023-02-17
Enrollment: 130
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Total Sleep Time
timeFrame: Post operative Day 0-2
Secondary outcomes:
measure: Postoperative Delirium Severity score
timeFrame: Postoperative Day 0 through Day 5
Other outcomes:
measure: Postoperative Average Electrographic Total Sleep Time Over the 3-night Recording Period
timeFrame: Postoperative day 0-2
measure: Average Postoperative Richards-Campbell Subjective Sleep Quality Scores
timeFrame: Postoperative days 1-5
measure: Change In Pupil Diameter Fluctuations From Preoperative Baseline Through Postoperative Day 3
timeFrame: Preoperative baseline and postoperative days 1-3
measure: Changes in Average Response Latency on Preoperative and Postoperative Psychomotor Vigilance Testing
timeFrame: Preoperative baseline, and postoperative days 1-3
measure: Postoperative Hospital Length of Stay
timeFrame: From Postoperative day 0 up to 4 week follow up visit
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Michael Devinney Jr, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: