Better Outcome With Melatonin Compared to Placebo Administered to Normalize Sleep-wake Cycle and Treat Hypoactive ICU Delirium The Basel BOMP-AID Randomized Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 190
- 试验地点
- 2
- 主要终点
- Duration of hypoactive delirium
研究概览
简要总结
Delirium is a neurobehavioural syndrome that frequently develops in the postoperative and/or ICU setting. The incidence of elderly patients who develop delirium during hospital stay ranges from 11-82%. Delirium was first described more than half a century ago in the cardiac surgery population, where it was already discovered as a state that might be accompanied by serious complications such as prolonged ICU and hospital stay, reduced quality of life and increased mortality. Furthermore, the duration of delirium is associated with worse long-term cognitive function in the general ICU population. This long-term experience with delirium suggests a high socioeconomic liability and has been a focus of many studies. The aforementioned consequences of delirium are observed in all of three subtypes: hypoactive, hyperactive, and mixed. Pharmacological treatment options for hypoactive delirium are lacking. Since patients in hypoactive delirium suffer from disturbed circadian rhythm, the investigators suggest that the administration of melatonin as a promising possibility in these patients to shorten delirium duration and to lower its severity. Previous investigations confirmed loss of melatonin rhythm in patients that had developed delirium thus reasoning the study hypothesis.
In this randomized study, the investigators aim to test the hypothesis that the reinstitution of a normal circadian rhythm by the administration of melatonin compared to placebo after diagnosis of hypoactive delirium, decreases the duration of delirium and reduces the transmission to a form of agitated delirium. The administration might have to be repeated several times to achieve resolution of delirium.
详细描述
Delirium is a neurobehavioural syndrome that frequently develops in the postoperative and/or ICU setting. The incidence of elderly patients who develop delirium during hospital stay ranges from 10-80%. Delirium was first described more than half a century ago in the cardiac surgery population, where it was already discovered as a state that might be accompanied by serious complications such as prolonged ICU and hospital stay, reduced quality of life and increased mortality. Furthermore, the duration of delirium is associated with worse long-term cognitive function in the general ICU population. This long-term experience with delirium suggests a high socioeconomic liability and has been a focus of many studies. Due to the multifactorial origin of delirium, there are several but no incontestable options for prevention and symptomatic treatment. Overall, delirium represents a high burden not only for the patient and his/her family members, but also for the medical care team that aims to prevent postoperative delirium to avoid serious consequences associated with it.
The aforementioned consequences of delirium are observed in all of three subtypes: hypoactive, hyperactive, and mixed. Many studies have been conducted to prevent and treat hyperactive and mixed delirium. Hypoactive delirium, suggested to be the most frequent form of delirium, is a different case: as it corresponds to a patient that is calm and as such doesn't cause any harm or inconvenience to himself or the caring medical team it also leads to two major problems. First, it is already known that hypoactive delirium is hard to detect. Second, because hypoactive delirious patients are calm or even asleep most of the time this delirium subtype doesn't go along with the same urge to become active in order to prevent harm. Also, pharmacological treatment usually addresses hyperactive and mixed delirium in standard operating procedures, whereas treatment of hypoactive delirium remains supportive. Pharmacological treatment options for hypoactive delirium are lacking. Since patients in hypoactive delirium suffer from disturbed circadian rhythm, investigators suggest that the administration of melatonin is a promising possibility in these patients to shorten delirium duration and to lower its severity. Previous investigations confirmed loss of melatonin rhythm in patients that had developed delirium thus reasoning the study hypothesis. Of note, melatonin is to be investigated for ICU delirium prevention in an Australian study, as the potential of chronotherapy to reduce delirium incidence has been suggested in a recently published article. The administration of dexmedetomidine to treat the disturbed circadian rhythm in hyperactive and mixed delirious ICU patients will be investigated in one of the investigators' current studies, but because of its sedative nature it clearly doesn't represent a treatment option for hypoactive delirium.
The aim of the BOMP-AID trial is to assess the superiority of melatonin to placebo for the treatment of hypoactive delirium in the ICU. The study hypothesis is based on the assumption that melatonin compared to placebo (Lactose monohydrate, cellulose powder, magnesium stearate (Ph. Eur.), mocrocristalline cellulose) administered at night restores a normal circadian rhythm, thus decreasing the duration of delirium and reducing the transmission to a form of agitated delirium.
Investigators would like to recruit 190 patients right after the diagnosis of hypoactive delirium. The administration might have to be repeated several times to achieve resolution of delirium.
After the first administration of melatonin or placebo at 8 p.m. investigators shall follow the standard operating procedure for hypoactive delirium for further treatment of delirium during daytime. In case of previously undiagnosed mixed delirium investigators are forced to follow the standard operating procedure for mixed delirium that includes the administration of haloperidol, quetiapine or trazodone. During the consecutive nightly hours the randomized study substance will be administered again if indicated. The latter will allow investigators to clearly detect the suggested shortening of delirium duration in the cohort where melatonin is being used as treating agent. Any use of drugs to treat forms other than hypoactive will be recorded.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants fulfilling all of the following inclusion criteria are eligible for the study:
- •Adult patients (aged 55 years or older)
- •Current delirium (hypoactive type) detected by a specialised assessment method: ICDSC score >2 and RASS score < 0
排除标准
- •Participants meeting the following criteria are excluded from the study:
- •Delirium prior to ICU admission
- •Sleep disorder not caused by hypoactive delirium
- •Sedation in the ICU
- •Hypersensitivity to the studied substances (i.e., melatonin, placebo content)
- •Age <55 years
- •Terminal state
- •Status epilepticus or postictal states following seizures on electroencephalogram (EEG)
- •Active psychosis
- •Substance abuse in current medical history
- •Pregnancy
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
Melatonin (Circadin ®)
干预措施: Melatonin (Circadin ®) (Drug)
结局指标
主要结局
Duration of hypoactive delirium
时间窗: From study inclusion to delirium resolution, assessed daily until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 28 days
Duration of hypoactive delirium in the ICU in 8-hour shifts
次要结局
- Number of ventilator days(From study inclusion until ICU discharge, assessed daily until the date of withdrawal of mechanical ventilation or date of death from any cause, whichever came first, assessed up to 28 days)
- Length of ICU stay(From ICU admission to ICU discharge, assessed daily until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 28 days)
- Sleep quality(From study inclusion until study termination, assessed daily until the date of first documented progression (i.e., delirium resolution) or date of death from any cause, whichever came first, assessed up to 28 days)
- Delirium-free days at 28 days after study inclusion(From study inclusion to ICU discharge, assessed up to 28 days)
- Death until day 28, day 90, and day 365 from ICU admission(Assessed at 28 days, 90 days, and 365 days after study inclusion)
- Length of hospital stay(From hospital admission to hospital discharge, assessed daily until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 90 days)