Ramelteon in the Prevention of Post-operative Delirium

Phase 2

Completed

Conditions: Cognitive Disorders
Delayed Emergence From Anesthesia
Delirium
Delirium, Dementia, Amnestic, Cognitive Disorders

Interventions: Drug: Ramelteon
Drug: Microcrystalline Cellulose
Drug: Riboflavin 100 mg

Brief Summary: This trial focuses on a Phase II randomized masked clinical trial testing the effectiveness and safety of peri-operative administration of ramelteon, a melatonin agonist in the prevention of postoperative delirium.

Detailed Description: This trial will randomize older aged patients undergoing general or regional anesthesia for orthopedic surgical procedures to three perioperative doses of a melatonin agonist, ramelteon, and placebo in a masked double blind fashion. The primary outcomes are 1) the incidence of post-operative delirium in the recovery period in the Postoperative Anesthesia Care Unit and on post-operative days 1 and 2 following surgery, and 2) the safety of ramelteon as documented by the presence of adverse events in the follow-up period.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Delirium diagnosis on the Confusion Assessment Method instrument at baseline
Is unable to give informed consent due to cognitive impairment and a suitable legally authorized representative (LAR) cannot be identified
Declines participation
Current medications that include:
1. ramelteon
2. melatonin
3. fluvoxamine
4. rifampin
5. ketoconazole
6. fluconazole
History of ramelteon or riboflavin intolerance
Heavy daily alcohol intake by medical record or history
Current moderate to severe liver failure (as defined by Charlson criteria
Evidence of Systemic Inflammatory Response Syndrome (SIRS) as measured by > 2 criteria8)
Presence of a condition that in the opinion of the PI compromises patient safety or data quality if enrolled in the study.

Arm && Interventions

Group	Intervention	Description
Treatment	Riboflavin 100 mg	Ramelteon 8 mg oral dose Riboflavin 100 mg (preoperative first dose only)
Placebo	Riboflavin 100 mg	Capsule Shells filled with microcrystalline cellulose Riboflavin 100 mg (preoperative first dose only - if received as an outpatient)
Treatment	Ramelteon	Ramelteon 8 mg oral dose Riboflavin 100 mg (preoperative first dose only)
Treatment	Microcrystalline Cellulose	Ramelteon 8 mg oral dose Riboflavin 100 mg (preoperative first dose only)
Placebo	Microcrystalline Cellulose	Capsule Shells filled with microcrystalline cellulose Riboflavin 100 mg (preoperative first dose only - if received as an outpatient)

Primary Outcome Measures

Name	Time	Method
Number of Participants With Delirium During Two Days Following Surgery	Up to Post Operative Day 2	Delirium DSM 5 based criteria informed by standardized history gathering, examination, cognitive evaluation using cognitive tests, informant interview, and medical record review) measured during Post-operative Day 1 and/or Day 2
Number of Participants With Delirium in the Post Anesthesia Care Unit (PACU)	Post Operative Day 0: Post Anesthesia Care Unit Following Recovery from Anesthesia	Delirium (DSM 5 based criteria informed by standardized history gathering, examination, cognitive evaluation using cognitive tests, informant interview, and medical record review) measured once recovered from anesthesia.

Secondary Outcome Measures

Name	Time	Method
Delirium Rating Scale - Revised- 98 (DRS-R98) in Delirious Patients	Postoperative Day 1 and Day 2	Measure Description: Delirium Rating Scale-Revised-98 (Severity items are rated on a scale of 0-3 and diagnostic items are rated on a scale of 0-2 or 0-3. The minimum score is 0. The maximum possible score for severity items is 39, while the maximum total score is 46. Higher scores indicate more severe delirium; score of 0 indicates no delirium.) Means and Standard Deviations were calculated from the maximum DRS-R98 score documented on Postoperative Day 1 and Day 2 for each participant who became delirious within each treatment arm.