Ramelteon in the Prevention of Post-operative Delirium (RECOVER)

Johns Hopkins University

Status and phase: Completed; Phase 2

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

Treatments: Drug: Microcrystalline Cellulose; Drug: Riboflavin 100 mg; Drug: Ramelteon

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02324153

1R21AG050850-01A1 (U.S. NIH Grant/Contract)

IRB00097232

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

• 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

Treatment

Experimental group

Description:

Ramelteon 8 mg oral dose Riboflavin 100 mg (preoperative first dose only)

Treatment:

Drug: Ramelteon

Drug: Riboflavin 100 mg

Drug: Microcrystalline Cellulose

Placebo

Placebo Comparator group

Description:

Capsule Shells filled with microcrystalline cellulose Riboflavin 100 mg (preoperative first dose only - if received as an outpatient)

Treatment:

Drug: Riboflavin 100 mg

Drug: Microcrystalline Cellulose