A Randomized Double Blind Placebo Controlled Trial of Ramelteon in the Prevention of Post-operative Delirium

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.

- Planned orthopedic surgery under general or regional anesthesia and post-operative
inpatient stay

- 65 years of age or older

- Mini-mental Status Exam (MMSE) score of 15 or greater prior to surgery;

- Ability to understand, speak, read and write English.

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.