Effects of Dexmedetomidine on Delirium Duration of Non-intubated ICU Patients (4D Trial)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 168
- 试验地点
- 2
- 主要终点
- duration of agitation (in hours), defined by a RASS ≥ +1
研究概览
简要总结
The primary purpose of the study is to evaluate whether dexmedetomidine is effective in treating agitated delirium of non-intubated ICI patients
详细描述
Delirium during intensive care unit (ICU) stay is frequent and associated with significant morbidity, mortality and healthcare related costs. International guidelines suggest its prevention. However, curative treatment remains unclearly established. Despite a non-unequivocal literature, haloperidol is the first line recommended neuroleptic. Dexmedetomidine, an alpha2-adrenergic receptors agonist has shown its efficiency in the treatment of delirium in intubated patients but also in its prevention. Dexmedetomidine represents a widely used alternative to haloperidol. Only few studies have compared the efficacy of dexmedetomidine in non-intubated ICU patients as a first line curative treatment of delirium. Main objective of 4D trial is to demonstrate that dexmedetomidine decreases delirium duration compared to placebo.
The 4D trial is an investigator-initiated, prospective, multicenter, randomized, double-blinded, two-arm trial, randomizing 300 non-intubated ICU patients with diagnosis of agitated delirium to receive dexmedetomidine or placebo as a cure. The primary outcome measure is a composite of duration of agitation or delirium or the use of intubation with deep sedation and mechanical ventilation. Secondary outcomes include mortalities at 7 and 28 days, ICU length of stay and occurrence of adverse effects. The sample size will allow the detection of a 50% decrease of agitation duration (120 minutes), of an absolute reduction of delirium duration (1 day) and of a 50% relative decrease of intubation and mechanical ventilation, with a type 1 error rate of 1.8 % (error risk inflation due to components of composite) and power of 90 %, assuming a 15 % incidence of intubation and mechanical ventilation requirements, an agitation duration of 240 minutes and a delirium duration of 3 days. One hundred and 10 patients by group will be needed. A intermediate analysis is scheduled and requires the inclusion of 150 patients in each group.
The 4D trial may provide important data on the safety of commonly used sedative dexmedetomidine and could have a significant impact on future treatment of non-intubated ICU patients presenting with agitated 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
- Double (Participant, Investigator)
盲法说明
double blind
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
- •• Age > 18 years
- •Patient hospitalized in an ICU
- •Presenting a productive delirium according to the following criteria:
- •acute onset (<2h) and fluctuating course during the same day
- •alteration of cognitive functions: disorganization of thought (delirium of persecution, inability to reason logically), abnormal perceptions (hallucinations), memory impairments, temporal disorientation, non- or misrecognitions, difficulties in naming objects or writing)
- •in whom a simple cropping and non-medicated therapeutics are not sufficient to allow symptoms' resolution for few hours
- •CAM-ICU positive AND a RASS > +1
- •Non-intubated or extubated (> 24h)
- •No contraindication of dexmedetomidine or haloperidol uses
排除标准
- •• Age <18 years
- •Administration of dexmedetomidine and/or clonidine during the 72 hours before inclusion
- •Contraindication to the use of Dexmedetomidine, clonidine or haloperidol (history of allergy, Parkinson's disease, oro-pharyngeal dysfunction, arterial hypotension or bradycardia, QTc interval prolongation, and hepatic or renal dysfunction), as mentioned in the Summaries of Product Characteristics
- •Neuropsychiatric pathology judged by the investigator as a potential source of bias (in particular: active drug addiction, psychosis...)
- •Parturient or breast-feeding woman
- •Protected major (guardianship)
- •Patient's or relative's refusal to participate
研究组 & 干预措施
dexmedetomidine
Patients in the Dexmedetomidine (interventional) group will be treated with a continuous infusion of dexmedetomidine in case of agitated delirium.
干预措施: Dexmedetomidine (Drug)
Normal Saline (NaCl 0.9%)
Patients in the Normal Saline (control) group will be treated with a continuous infusion of normal saline in case of agitated delirium.
干预措施: Placebo (Other)
结局指标
主要结局
duration of agitation (in hours), defined by a RASS ≥ +1
时间窗: at day 1
delay (in hours) between inclusion and intubation requirement to control delirium with deep sedation and mechanical ventilation
时间窗: at day 1
requirement of intubation to control delirium with deep sedation and mechanical ventilation
duration of delirium (in days), defined by a positive CAM-ICU
时间窗: at day 1
次要结局
- Number of ventilator free days(at day 30)
- Occurrence of hypotension requiring any vasopressor administration(at day 30)
- Duration of mechanical restraint prescribed and carried out(at day 30)
- All-cause mortality(at day 7)
- Adverse effects such as the occurence of pneumonia (following the ATS definitions) and/or septicemia(at day 30)
- Length of ICU stay (in days)(at day 1)
- Occurrence of tachycardia(at day 30)