Clinical and Genomic Responses to Open Heart Surgery: A Randomized Controlled Trial of the Effects of Remote Ischemic Preconditioning
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Impact of RIPC on length of hospital stay.
研究概览
简要总结
This study will be the first large scale randomized study of remote ischemic preconditioning (RIPC) ever performed and will define the role of this novel therapy as a clinical tool. This study will also be the first to define preoperative gene expression profiles associated with poor postoperative outcomes in a control (SHAM) population of children undergoing cardiac surgery. Finally, the role of RIPC in modifying these gene expression profiles will be examined. Therefore, mechanistic insight into the proven ability of RIPC to improve markers of tissue injury, and the expected improvement in clinically relevant endpoints, will be examined.
详细描述
Remote ischemic preconditioning (RIPC) is a powerful, innate mechanism of protection against ischemia-reperfusion (IR) injury. During the course of previous investigations, it was shown in animal models that transient limb ischemia (our stimulus for generating remote ischemic preconditioning) leads to induction of a portfolio of myocardial genomic responses concerned with stress-response and repair mechanisms, reduces myocardial infarction after prolonged coronary occlusion, protects against cardiopulmonary bypass-induced neural, pulmonary and myocardial damage, and when administered to the recipient, reduces IR injury in the transplanted heart.
In humans, it has been have shown that RIPC downregulates genes responsible for pro-inflammatory pathways concerned with TNFα-signaling, apoptosis and exocytosis in circulating leukocytes, reduces ischemia-induced endothelial dysfunction, and decreases markers of myocardial and lung injury in a pilot study of children undergoing open heart surgery. However, the latter study was not powered to demonstrate differences in anatomic and age-related subgroups, or clinically relevant 'hard' end-points such as ventilation time, intensive care, and length of hospital stay.
Thus, we are now proposing a large-scale clinical study examining genetic predictors of clinically relevant postoperative outcomes, and how they are modified by remote preconditioning.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Day 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject age birth (>36 weeks gestation) to 17 years.
- •Underlying cardiac anatomy and planned primary repair with no anticipated residual shunting. Repair must necessitate use of cardiopulmonary bypass.
- •Informed consent/assent of subject, parent(s) or legal guardian as appropriate.
排除标准
- •Current or recent ischemic insult, defined as vascular occlusion or episode of cardiorespiratory collapse requiring medical intervention occurring within 7 days of enrollment.
- •Evidence in any system for organ dysfunction that requires medical intervention.
- •Current treatment with systemic anticoagulation therapy or the presence of a bleeding diathesis.
- •Presence of important pulmonary or airway disease requiring medical intervention.
- •Current or previous (within 10 days of screening) use of systemic corticosteroids.
- •Recent (within 7 days of screening) or current documented systemic infection or sepsis.
- •Anticipated unavailability of an uninstrumented limb with no anatomic or physiologic abnormality precluding administration of RIPC stimulus using a standard blood pressure cuff.
研究组 & 干预措施
1
干预措施: Remote ischemic preconditioning (RIPC) (Procedure)
2
干预措施: SHAM (Procedure)
结局指标
主要结局
Impact of RIPC on length of hospital stay.
时间窗: Assessed through post-operative hospitalization.
次要结局
- Gene expression patterns associated with effects of RIPC.(Assessed and recorded during the first 24 hours after surgery.)
- Neurodevelopmental Outcomes (Age 2-6 years old at surgery)(Follow-up at 12-18 months post-surgery)
- Patterns of baseline gene expression predictive of the clinical and physiologic impact of cardiopulmonary bypass in children (SHAM group only).(Assessed and recorded during the first 24 hours after surgery.)
- Impact of RIPC on clinical and physiologic markers related to ischemia-reperfusion injury after cardiac surgery in children.(Assessed and recorded serially during the first 48 hours after surgery.)
- Neurodevelopmental Outcomes (Age < 2 years old at surgery)(Follow-up at 12-18 months post-surgery)
研究者
Brian McCrindle
Staff Cardiologist
The Hospital for Sick Children