Delirium Reduction With Ramelteon

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Delirium Reduction With Ramelteon

Conditions
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Delirium

Intervention / Treatment
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* Drug: Ramelteon 8mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, double-blinded, placebo controlled
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |