Efficacy of Haloperidol to Decrease the Burden of Delirium in Adult Critically Ill Patients (EuRIDICE): a Prospective Randomised Multi-center Double-blind Placebo-controlled Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 142
- 试验地点
- 8
- 主要终点
- delirium- and coma-free days
研究概览
简要总结
The EuRIDICE trial will study whether haloperidol as a first line treatment for ICU delirium reduces delirium duration (and severity). Adverse outcomes typically associated with delirium will also be studied and include long term cognition, functional outcome and quality of life. Further, patient and family experiences and cost-effectiveness will be assessed. Finally, safety concerns associated with the use of haloperidol in this vulnerable population will be studied.
详细描述
BACKGROUND. Although widely used, the efficacy and safety of haloperidol for delirium in critically ill adults remain unclear. A randomised controlled trial is warranted to study the effect of haloperidol on delirium or coma, long-term outcomes, safety concerns, and cost-effectiveness.
SUMMARY.
The investigators will perform a multi-center, randomised, double-blind, placebo-controlled clinical trial to evaluate the use of haloperidol for delirium treatment in 742 critically ill adults with delirium. Days spent without delirium- or coma in the first 14 days after randomisation is the primary outcome. Study drug will be initiated at 2.5mg IV q8h and increased after 24 hours to 5mg IV q8h if delirium persists. Study drug dose will be tapered when delirium has resolved during 24 hours. All patients will be managed with a standardized pain, agitation and delirium protocol. Standard operating procedures for agitation (analgesia titration, alpha2 agonists) and hallucination management (atypical antipsychotics) will be implemented to accommodate possible imbalances of these symptoms in both treatment arms. Open-label haloperidol administration is discouraged during the trial. The sample size provides a power of 90% to detect statistically significant results (p<.05) and a true treatment difference of one day for the primary outcome between trial arms.
This trial is expected to answer the clinically relevant question whether haloperidol still deserves a place in ICU delirium management. The primary outcome (delirium- and coma-free days) will be related to the secondary outcomes cognitive dysfunction, functional and psychological outcomes and patient- and family experiences. An extensive cost-effectiveness analysis will be done. Mortality at one year and safety concerns of haloperidol (QTc prolongation on EKG and rigidity) will be assessed as secondary endpoints. In conclusion, this large multicentre trial will assess efficacy and safety of haloperidol for ICU delirium.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
placebo and haloperidol (verum) will have the same appearance
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
haloperidol
study drug will be titrated based on delirium, diagnosed with a validated screening instrument (CAM-ICU or ICDSC), starting with 2.5mg IV q8h and titrated to a maximum of 5mg IV q8h.
Agitation and hallucinations will be managed according to a pre-specified protocol in both treatment arms. First the study drug will be increased when agitation or delirium remain present. Further options include mainly the use of alfa-2 agonists (agitation) or atypical antipsychotic drugs (hallucinations).
干预措施: Haloperidol (Drug)
placebo
study drug will be titrated based on delirium, diagnosed with a validated screening instrument (CAM-ICU or ICDSC), starting with 2.5mg IV q8h and titrated to a maximum of 5mg IV q8h.
Agitation and hallucinations will be managed according to a pre-specified protocol in both treatment arms. First the study drug will be increased when agitation or delirium remain present. Further options include mainly the use of alfa-2 agonists (agitation) or atypical antipsychotic drugs (hallucinations).
干预措施: Placebo (Drug)
结局指标
主要结局
delirium- and coma-free days
时间窗: within the first 14 days after randomisation
days without brain dysfunction (=delirium OR coma) while at the ICU
次要结局
- Cognitive deterioration: Cognitive flexibility(3 and 12 months)
- mortality(28 days and 1 year)
- Patients' and family-members' experiences related to delirium(at discharge from hospital (up to a maximum of 12 months after randomisation = end of follow-up period) and 3 months after randomisation)
- Cognitive deterioration: Semantic fluency(3 and 12 months)
- length of stay at ICU(days of ICU stay (time in days from ICU admission until ICU discharge). Assessed up to a maximum of 12 months after randomisation (end of follow-up period).)
- Adverse drug associated events: prolonged QTc by EKG(while on study drug treatment during study period at ICU (up to 14 days after randomisation))
- Cognitive deterioration: Global cognitive functioning(3 and 12 months)
- Cognitive deterioration: Working memory(3 and 12 months)
- Cognitive deterioration: Word retrieval(3 and 12 months)
- Anxiety and depression(3 and 12 months)
- Adverse drug associated events: ventricular arrhythmia's(during study period at ICU (up to 14 days after randomisation))
- Functional outcome(3 and 12 months)
- Adverse drug associated events: muscle rigidity and other associated movements disorders(while on study drug treatment during study period at ICU (up to 14 days after randomisation))
- Cognitive deterioration: Verbal learning and memory(3 and 12 months)
- Patients' memories related to their ICU stay(at discharge from hospital (up to a maximum of 12 months after randomisation = end of follow-up period) and 3 months after randomisation)
- Posttraumatic stress syndrome(at 3 months after randomisation)
- Caregiver Strain(at 3 months after randomisation)
研究者
Mathieu van der Jagt
Principal Investigator / Medical Doctor, PhD
Erasmus Medical Center