Delirium Reduction With Ramelteon (DREAM)

The overall purpose of this study is to identify a medication that might treat and/or prevent delirium in intensive care unit (ICU). Currently, there is no proven medical therapy for prevention or treatment of delirium. Ramelteon is a medication approved for insomnia. We hypothesize that ramelteon may help regulate the day/night cycle and decrease ICU delirium.

Study Overview

• Status: Recruiting
• Conditions: Delirium
• Intervention / Treatment: Drug: Ramelteon 8mg

Detailed Description

Melatonin is an endogenous hormone that regulates the sleep-wake cycle along with several other physiological functions. It is reported that melatonin secretion may be impaired in ICU patients, and there is some question whether this may be a contributing factor to delirium occurrence. Ramelteon is a melatonin agonist with three to six times increased affinity for MT1 and MT2 receptors versus melatonin. It is FDA approved for the treatment of insomnia, and some studies suggested some benefit with ramelteon for delirium prevention. There is limited prospective research data assessing the efficacy of ramelteon for delirium treatment. The goal of this study therefore is to assess the efficacy of ramelteon versus placebo on the prevention and treatment of delirium in ICU patients.

• Study Type: Interventional
• Enrollment (Estimated): 506
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jennifer Johnson, MD; Phone Number: 214 604-8665; Email: jennifer.johnson19@hcahealthcare.com
• Study Contact Backup: Name: Chelsea Mitchell, PharmD; Phone Number: 615 342-4725; Email: chelsea.mitchell@hcahealthcare.com

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • Recruiting
      • Centennial Medical Center
      • Contact: Jennifer Johnson, MD; Phone Number: 214-604-8665; Email: jennifer.johnson19@hcahealthcare.com
      • Contact: Chelsea Mitchell, ParmD; Phone Number: 6153424725; Email: chelsea.mitchell@hcahealthcare.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Medical or surgical ICU patient
• Ability to take oral or nasogastric tube within 48 hours of admission to ICU
• Expected ICU length of stay and life expectancy at least 48 hours
• Patient or POA capable of signing informed consent within 48 hours of ICU admission

Exclusion Criteria:

• Past medical history includes cirrhosis
• Active alcohol withdrawal
• Patients taking fluvoxamine prior to admission
• Self-reported hypersensitivity to ramelteon
• Incarcerated patients
• Pregnant patients
• Patients with acute neurological conditions including brain abscess, head bleed, meningitis
• Patients who are transferred from an outside hospital where they have resided for greater than 4 days
• Non-English speaking patients
• Hearing-impaired patients requiring sign language for communication
• Visually-impaired patients

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ramelteon; ramelteon 8 mg crushed tablet daily at 20:30	Drug: Ramelteon 8mg; administered crushed, orally at 20:30
Placebo Comparator: placebo; placebo powder equivalent grams at 20:30	Drug: Ramelteon 8mg; administered crushed, orally at 20:30

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days alive without delirium or coma in the ICU	joint modeling approach taking account recurrence and terminating events	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean daily Confusion Assessment Method -7 CAM-ICU-7 score	Mean CAM-ICU-7 score	14 days
Incidence of delirium, as defined by a positive CAM-ICU-7	Incidence	14 days
Mortality at 14 days from randomization or hospital discharge	Mortality	14 days
Duration of delirium, defined as number of days CAM-ICU positive	Duration	14 days
ICU length of stay	LOS	14 days

Collaborators and Investigators

• Sponsor: Centennial Medical Center
• Investigators: Principal Investigator: Jennifer Johnson, MD, Centennial Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: September 25, 2021
• First Submitted That Met QC Criteria: September 25, 2021
• First Posted (Actual): October 6, 2021

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: August 20, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium
• Other Study ID Numbers: 2021-438

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.: Yes