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

June 16, 2020 updated by: Johns Hopkins University

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins Bayview Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment
Ramelteon 8 mg oral dose Riboflavin 100 mg (preoperative first dose only)
Drug: Ramelteon
1 pre-operative and 2 nightly postoperative doses of Ramelteon/placebo will be administered
Other Names:
  • Rozerem
Drug: Microcrystalline Cellulose
Placebo Comparator
Drug: 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)
Other Names:
  • Adherence marker
Placebo Comparator: Placebo
Capsule Shells filled with microcrystalline cellulose Riboflavin 100 mg (preoperative first dose only - if received as an outpatient)
Drug: Microcrystalline Cellulose
Placebo Comparator
Drug: 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)
Other Names:
  • Adherence marker

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Delirium During Two Days Following Surgery
Time Frame: 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
Up to Post Operative Day 2
Number of Participants With Delirium in the Post Anesthesia Care Unit (PACU)
Time Frame: 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.
Post Operative Day 0: Post Anesthesia Care Unit Following Recovery from Anesthesia

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Delirium Rating Scale - Revised- 98 (DRS-R98) in Delirious Patients
Time Frame: 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.
Postoperative Day 1 and Day 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Aging (NIA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Karin J Neufeld, MD MPH, Professor - Department of Psychiatry and Behavioral Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 24, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 26, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 26, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 15, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 18, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 24, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 30, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 16, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00097232
  • 1R21AG050850-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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