Ramelteon Prevention of Delirium - RCT

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.

Inclusion Criteria:

- from designated nursing units

Exclusion Criteria: