Ramelteon in the Prevention of Post-operative Delirium

A Randomized Double Blind Placebo Controlled Trial of Ramelteon in the Prevention of Post-operative Delirium in Older Patients Undergoing Orthopedic Surgery

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.

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.