Prophylactic Haloperidol Use for Delirium in ICU Patients; a Randomized Placebo-controlled Double-blind Multicentre Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 1,800
- 试验地点
- 1
- 主要终点
- All cause mortality
研究概览
简要总结
The aim of this study is to determine the effects of a low dosage of prophylactic haloperidol in patients with a high risk to develop delirium, defined by an expected ICU length of stay of >1 day. The investigators hypothesized that haloperidol prophylaxis in patients with a high risk for delirium reduces 28-day mortality, delirium and delirium related outcome.
Two different dosages of haloperidol are used in this study to compare with placebo. A dosage of 1mg, or 2mg or placebo three times a day in a double-blinded fashion resulting in a three-armed multicentre randomized double-blinded placebo-controlled trial. To relate the potential beneficial effects of haloperidol to the a priori risk to develop delirium, the PREDELIRIC-model (delirium prediction model for ICU patients) will be used. This will enable the investigators to determine the preventive efficacy of haloperidol in patient groups based on their risk to develop delirium.
详细描述
In this study high risk patients will be included. Based on historical data the investigators know that the median predicted delirium risk is 35% in patients with an expected stay on the ICU of over one day. This is considered a high risk to develop delirium.
To assess patients for delirium using the Confusion Assessment Method (CAM)-ICU is part of daily clinical practice in all participating centres. In this study, high risk patients will receive three times a day a study drug of which two groups receive a low dose of haloperidol (1mg or 2mg) and a third arm will receive placebo.
This drug is worldwide the first choice of drug to treat delirious patients. When delirium is diagnosed, patients are treated according to delirium protocol, using a higher dosage than in the prophylactic treatment period as described in the study protocol. It is recognized that early treatment of delirium has beneficial effects compared with delayed treatment, and there is also some evidence that delirium prevention in ICU patients has beneficial effects, but the design of these previous studies was not optimal.
Potential side-effects of haloperidol include, extrapyramidal symptoms, drowsiness, agitation, and ventricular arrhythmias. The latter are extremely rare (only case-reports are published) and related to a higher dosage of haloperidol. With the dosage that will be used in the present study no relevant side-effects are anticipated. Nevertheless, and given the preventive nature of this study, extra attention is being paid on recognition of possible side-effects of haloperidol in the protocol. Importantly, in three recent prophylactic haloperidol studies no relevant side-effects, and in particular no ventricular arrhythmias, were reported using a similar low dosage of haloperidol as described in the present protocol.
During the study several inter-rater reliability checks (delirium experts versus ICU nurses) concerning the CAM_ICU assessments will be performed. Also medical and nursing files will be checked to secure the quality of the delirium diagnose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •expected length of ICU stay of over one day
排除标准
- •history of epilepsy, Parkinson's disease, hypokinetic rigid syndrome, dementia or alcohol withdrawal syndrome
- •patients admitted to the ICU for neurological reasons (including post-resuscitation patients)
- •patients treated with other anti-psychotics
- •prolonged QTc-time (>500msec) or history of serious ventricular arrhythmia (in last 12 months)
- •pregnancy/breast feeding
- •delirious before ICU admission
- •serious auditory or visual disorders
- •ICU-stay ≤1 day
- •unable to understand Dutch
- •severely mentally disabled
- •serious receptive aphasia
- •moribund and not expected to survive 2 days
- •known allergy to haloperidol
研究组 & 干预措施
Haloperidol 1mg/q8h
Prophylactic haloperidol of 1 mg/q8h i.v.
干预措施: Haloperidol 1 mg/q8h (Drug)
Haloperidol 2mg/q8h
Prophylactic haloperidol 2mg/q8h i.v.
干预措施: Haloperidol 2 mg/q8h (Drug)
Sodium chloride 0.9%
Placebo (Sodium chloride 0.9%) three times a day
干预措施: Placebo (Drug)
结局指标
主要结局
All cause mortality
时间窗: 28-day
Number of days of survival in 28-days after inclusion.
次要结局
- Number of delirium free days(28 days)
- Delirium related outcome during ICU stay(up to 28 days)
- Determining efficacy in different risk groups(up to 28 days)
- Delirium incidence during ICU stay(up to 28 days)
- Side effects of haloperidol prophylaxis during prophylactic treatment(up to 28 days)
- All cause mortality(90 day)