Ramelteon Prevention of Delirium - RCT

Study Overview
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Brief Summary
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Delirium is a common morbid condition in hospitalized adults. Treatment of delirium has been unsatisfactory and prevention is the preferred goal. Based on limited experimental research, ramelteon appears to have promise for prevention. This study will evaluate ramelteon in prevention of delirium in a hospitalized adult population age 65+ in a double-blinded RCT.

Detailed Description
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Delirium is a very common condition that is associated with significant complications in hospitalized adults. The manifestations of delirium are the result of a disturbance of brain functioning, the causes of which include a very wide array of illnesses, intoxications, and stresses. Delirium has been estimated to affect 20-50% of hospitalized patients, and to be associated with longer hospital stay (2x), greater likelihood of discharge to nursing home (2x), and higher rate of death (2x). 20% have delirium on admission. Patients who experience delirium may have persistent confusion (cognitive impairment). In 20%, this confusion appears to be permanent. Treatment of delirium has been unsatisfactory. Once it develops, no therapy or intervention has demonstrated a meaningful reduction of delirium associated complications. Prevention is clearly the preferred goal. Based on limited reports, ramelteon appears to have the most promise for prevention. Ramelteon, FDA approved (2005) as a nonscheduled prescription hypnotic agent, is generally considered safe and effective with no serious associated side effects, and no limitation of duration of use. It is related to melatonin in action and shares sleep promoting effects (reduced sleep latency) and improvement in coordination of circadian cycles. A recent randomized placebo-controlled single blinded trial of ramelteon treated 33 patients with ramelteon 8 mg/d. The researchers reported that ramelteon was associated with a dramatically lower risk of delirium (3% vs 32%; P = .003), with a relative risk of 0.09. Estimates of time to develop delirium were delayed for ramelteon compared to placebo, and the frequency of delirium was significantly lower in ramelteon compared to placebo (P = .002). There were significant limitations of this study, however, including a very high exclusion rate (1059 of 1126 [94%] patients assessed were excluded), a 24+ hour delay in initiation of study agent, a small sample size, and unclear sampling bias. The investigators propose a clinical trial of ramelteon to prevent delirium in patients admitted to Hartford Hospital. Hartford Hospital is in a unique position to conduct this study having established the ADAPT program to systematically apply best practices to the assessment and management of delirium. A registry of patients screened contains all of the screening results (over 1.5 million CAM screens on nearly 91,000 patients). Our study will permit us to evaluate the recent limited research findings regarding ramelteon in a larger general adult hospitalized population, and evaluate the potential benefit of treatment started earlier in the course of a hospitalization.

Official Title
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Randomized, Double Blind, Placebo-Controlled Clinical Trial Evaluating Ramelteon in the Prevention of Delirium

Conditions
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Delirium

Intervention / Treatment
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* Drug: ramelteon
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: from designated nursing units Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ramelteon<br>receive ramelteon | Drug: ramelteon<br>* double-blind RCT<br>* Other names: Rozerem;|
| Placebo Comparator: placebo<br>receive placebo | Drug: Placebo<br>* double-blind RCT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| delirium | delirium as determined by CAM screening and expert review | through study completion, anticipate completion at 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prevention