Alpha 2 Adrenergic Receptor Agonists for the Prevention of Delirium and Cognitive Decline After Open Heart Surgery (ALPHA2PREVENT): Randomised Controlled Trial.
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 900
- 试验地点
- 5
- 主要终点
- Postoperative delirium
研究概览
简要总结
A parallel-group treatment, five-centre, participant and investigator masked, three-arm study to assess the safety and effectiveness of dexmedetomidine or clonidine infusion compared to placebo for the prevention of delirium and cognitive decline in male and female participants aged 70+ scheduled for open heart surgery.
详细描述
Delirium is a major public health concern without therapeutic options. It is an acute disturbance of attention and cognition, precipitated by an acute somatic condition. Delirious patients are often subject to off-label treatment with psychotropic drugs that have dubious effects.
The intravenous alpha-2-adrenergic receptor agonist dexmedetomidine, attenuating sympathetic nervous system activity, shows promise as treatment for delirium, but its use is limited to intensive care units (ICU). Its long-term cognitive effects are unknown. Clonidine is a pharmacodynamically similar drug that can be given orally and has been used for decades as an antihypertensive agent, but is else sparsely studied.
ALPHA2PREVENT will be a three-armed randomised controlled trial to study 1) whether repurposing of clonidine can represent a novel treatment option for delirium, and 2) the possible effects of both dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns, patient rated outcome measures and biomarkers of neuronal injury.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants are eligible to be included in the study only if all of the following criteria apply:
- •Participant must be ≥70 years old at the time of signing the informed consent.
- •Participant must be accepted for cardiac surgery with cardiopulmonary bypass. The surgical procedures may constitute 1) coronary bypass grafting, 2) tricuspid, mitral, or aortic valve replacement or repair, 3) surgery on the ascending aorta, and 4) the combination any of these procedures.
- •Participant must be capable of giving signed informed consent.
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Preoperative delirium
- •Known hypersensitivity to the active ingredient or components of the product
- •Bradycardia due to sick-sinus-syndrome, 2nd or 3rd degree AV-block (if not treated with pacemaker) or any other reason causing HR <50 bpm at time of inclusion
- •Uncontrolled hypotension
- •Ischemic stroke or transitory ischemic attack the last month or critical peripheral ischemia
- •Acute coronary syndrome last 24 hours. Acute coronary syndrome is defined according to international guidelines
- •Left ventricular ejection fraction < 40%
- •Severe renal impairment (estimated GFR <20ml/min) or expected requirement for renal replacement therapy
- •Severe hepatic dysfunction (liver enzyme three times the upper limit of normal together with a serum albumin concentration below the normal reference limit)
- •Reduced peripheral autonomous activity (e.g. spinal cord injury)
- •Current use of tricyclic antidepressants, monoamine reuptake inhibitors or ciclosporin
- •Endocarditis or sepsis
- •Pheochromocytoma
- •Planned deep hypothermia and circulatory arrest
- •Emergency surgery, defined as less than 24 hours from admission to surgery
- •Previously included in this study
- •Not speaking or reading Norwegian
- •Any other condition as evaluated by the treating physician
研究组 & 干预措施
Dexmedetomidine (D)
Continuous intravenous infusion of dexmedetomidine 0.4 μg/kg/hour from the start of cardiopulmonary bypass and during surgery, followed by 0.2 μg/kg/hour until discharge from the ICU or 24 hours postoperatively, whichever happens first.
干预措施: Dexmedetomidine (Drug)
Clonidine (C)
Continuous intravenous infusion of clonidine 0.4 μg/kg/hour from the start of cardiopulmonary bypass and during surgery, followed by 0.2 μg/kg/hour until discharge from the ICU or 24 hours postoperatively, whichever happens first.
干预措施: Clonidine (Drug)
Placebo (P)
Continuous intravenous infusion of saline 0.4 μg/kg/hour from the start of cardiopulmonary bypass and during surgery, followed by 0.2 μg/kg/hour until discharge from the ICU or 24 hours postoperatively, whichever happens first.
干预措施: Natriumchlorid (Drug)
结局指标
主要结局
Postoperative delirium
时间窗: Up to 7 days
Cumulative incidence of postoperative delirium, as diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria
次要结局
- Incidence of coma(Up to 7 days)
- Incidence of death, coma or postoperative delirium(Up to 7 days)
- Number of delirium days postoperatively(Up to 7 days)
- Delirium severity(Up to 7 days)
- Motor activity patterns(6 months)
- Change in cognitive function between inclusion and after 1 and 6 months(6 months)
- Change in patient rated health status between inclusion and after 1 and 6 months(6 months)
- Serum concentrations of NFL and p-tau181(5 days postoperatively)
- Estimate associations between frailty and the other endpoints(6 months)
- Safety and tolerability(6 months)
- Interaction between preoperative frailty and treatment on delirium and the other endpoints(6 months)
- Change in frailty status between inclusion and after 1 and 6 months(6 months)
- Comparison of change in frailty status between inclusion and after 1 and 6 months(6 months)
研究者
Bjørn Erik Neerland, MD
Medical doctor, postdoctoral researcher
Oslo University Hospital