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临床试验/NCT02177981
NCT02177981已完成不适用

A Randomized, Double-Blind, Controlled Clinical Trial: Impact of Remote Ischemic Preconditioning Preceding Coronary Artery Bypass Grafting on Inducing Neuroprotection

University of Zagreb1 个研究点 分布在 1 个国家目标入组 70 人开始时间: 2014年3月1日最近更新:
适应症
干预措施

试验速览

阶段
不适用
状态
已完成
入组人数
70
试验地点
1
主要终点
Composite structural and functional neurological outcome

研究概览

简要总结

Coronary artery disease (CAD) is the leading cause of death worldwide. Patients with severe CAD are often treated with coronary artery bypass grafting (CABG). Novel treatment strategies need to be pursued to respond to the continuous increase in the risk profile of contemporary CABG patients. Surgical myocardial revascularization is commonly performed with the use of cardiopulmonary bypass (CPB). Neurological impairment following CABG may take on the form of a new-onset motor deficit or postoperative cognitive dysfunction. The former is rare, but potentially devastating. Conversely, declines in attention, memory and fine motor skills can frequently be documented.

Ischemic preconditioning is a phenomenon of an endogenous protective response to organ ischemia, which is triggered by brief cycles of nonlethal ischemia and reperfusion in tissues known to be more resistant to ischemic insults. In clinical practice remote ischemic preconditioning (RIPC) is achieved by inflicting short periods of ischemia with intermittent restitution of flow to the upper extremity. This intervention has been shown to be effective in the reduction of myocardial injury in cardiac surgical patients. The hypothesis tested in this research proposal is that RIPC will decrease the extent of postoperative neurological injury following CABG.

In this research project, 70 patients scheduled for an elective CABG will be recruited at a single center. They will be randomly allocated to either undergo RIPC (intervention arm) or a sham procedure (control arm). Inflating a blood pressure cuff to 200 mmHg for 5 min will induce RIPC, thereby inducing a brief period of ischemia. This will be followed by a 5-minute arm reperfusion. In total, three cycles of arm ischemia and reperfusion will be induced in this fashion.

All patients will undergo pre- and post-procedural magnetic resonance imaging (MRI) of the brain, as well as neurocognitive testing. The array of MRI tools that will be used for the quantification of brain injury will include fluid attenuated inversion recovery, diffusion weighted and susceptibility weighted imaging, coupled with resting state functional MRI.

The investigators aim to determine whether RIPC can reduce the adverse impact of CPB on neurological outcome as evaluated by MRI detectable brain ischemia and neurocognition.

详细描述

Coronary artery bypass grafting (CABG) is very effective in the management of complex coronary artery disease (CAD). Cardiopulmonary bypass (CPB) is commonly employed to achieve a still and bloodless field, which facilitates the creation of technically impeccable coronary anastomoses. Multiple adverse effects that stem from exposure of blood to a non-endothelial surface contrast the clear benefit of CPB. Neurological damage remains one of the most dreaded complications following CABG. While the incidence of new focal motor deficits is low, postoperative neurocognitive dysfunction (POCD) is seen commonly. The increasing risk profile of contemporary CABG patients makes neuroprotective strategies progressively more important.

Ischemic preconditioning is an endogenous protective response triggered by brief episodes of nonlethal ischemia and reperfusion. In clinical practice remote ischemic preconditioning (RIPC) is achieved by inducing short periods of ischemia of the upper extremity, followed by restitution of flow. This non-pharmacological strategy for inducing ischemic tolerance is cost-free and non-invasive, with potentially wide clinical applicability.

The "Impact of Remote Ischemic Preconditioning preceding Coronary Artery bypass Grafting on inducing nEuroprotection (RIPCAGE) trial" will recruit 70 patients scheduled for elective CABG at a single academic center. The hypothesis tested in this research proposal is that RIPC will decrease the extent of postoperative neuronal damage and lead to a reduction in POCD among CABG patients. Specifically, the investigators aim to determine whether RIPC can reduce magnetic resonance imaging (MRI) detectable brain damage and attenuate the neurocognitive decline universally seen in patients after CABG.

The primary composite outcome will consist of a composite of new ischemic lesions on brain MRI and POCD.

The secondary endpoints will be the following:

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
Triple (Participant, Investigator, Outcomes Assessor)

入排标准

年龄范围
18 Years 至 80 Years(Adult, Older Adult)
性别
All
接受健康志愿者
否

入选标准

  • •Adult patients with multi-vessel coronary artery disease undergoing primary, elective on-pump CABG
  • •Written informed consent

排除标准

  • •Prior stroke, transient ischemic attack or reversible ischemic neurologic deficit
  • •Stenosis of the internal carotid artery (>50%)
  • •Significant peripheral arterial disease affecting the upper limbs
  • •Acute coronary syndrome within 30 days prior to surgery
  • •Inability to provide consent
  • •Postoperative exclusion criteria will be limited to contraindications to follow-up MRI (such as pacemaker dependence)

研究组 & 干预措施

Remote ischemic preconditioning

Active Comparator

A blood pressure cuff will be placed on the left arm and three cycles of 5 min ischemia followed by 5 min reperfusion will be applied.

干预措施: Remote ischemic preconditioning (Procedure)

Control

Sham Comparator

The cuff will be placed around the arm but not inflated.

干预措施: Control (Procedure)

结局指标

主要结局

Composite structural and functional neurological outcome

时间窗: 7 days

New ischemic lesions on brain MRI and postoperative neurocognitive dysfunction

次要结局

  • Peri-operative brain injury(7 days)
  • Postoperative neurocognitive decline(7 days)
  • Brain connectivity profiles(7 days)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Hrvoje Gasparovic, MD, PhD

Associate professor

University of Zagreb

研究点 (1)

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