Ramelteon in the Prevention of Post-operative Delirium

Delirium Clinical Trial

— RECOVER  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02324153
• Other study ID #: IRB00097232
• Secondary ID: 1R21AG050850-01A
• Status: Completed
• Phase: Phase 2
• Start date: March 24, 2017
• Est. completion date: June 26, 2019

Study information

• Verified date: June 2020
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: June 26, 2019
• Est. primary completion date: June 26, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

• 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.

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Disorders
• Delayed Emergence From Anesthesia
• Delirium
• Delirium, Dementia, Amnestic, Cognitive Disorders
• Disease
• Neurocognitive Disorders

Intervention

Drug:
• Ramelteon
1 pre-operative and 2 nightly postoperative doses of Ramelteon/placebo will be administered
• Microcrystalline Cellulose
Placebo Comparator
• Riboflavin 100 mg
Riboflavin will be added to both placebo and active intervention capsules in order to track adherence to dose while taken as an outpatient (i.e. only the first preoperative dose)

Locations

Country	Name	City	State
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Delirium During Two Days Following Surgery	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	Up to Post Operative Day 2
Primary	Number of Participants With Delirium in the Post Anesthesia Care Unit (PACU)	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.	Post Operative Day 0: Post Anesthesia Care Unit Following Recovery from Anesthesia
Secondary	Delirium Rating Scale - Revised- 98 (DRS-R98) in Delirious Patients	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.	Postoperative Day 1 and Day 2