NCT00650507

Clinical and Genomic Responses to Open Heart Surgery

Clinical and Genomic Responses to Open Heart Surgery: A Randomized Controlled Trial of the Effects of Remote Ischemic Preconditioning

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 300 (actual)
• Sponsor: The Hospital for Sick Children · Academic / Other
• Sex: All
• Age: 1 Day – 17 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Ischemia-reperfusion (IR) Injury

Interventions

Type	Name	Description
PROCEDURE	Remote ischemic preconditioning (RIPC)	The RIPC stimulus will be delivered in the OR prep room after the induction of anesthesia (while the anesthesiologist and staff are inserting vascular cannulae and preparing the patient for surgery). Whenever possible, the left lower limb will be selected for delivery of the stimulus. An appropriate sized cuff will be selected and connected to a hand aneroid sphygmomanometer. A second cuff and hand aneroid sphygmomanometer will be placed beside the one connected to the study subject. The cuff on the limb will be inflated and deflated to provide a total of four cycles of limb ischemia and reperfusion.
PROCEDURE	SHAM	For this group, the procedure will be identical for that described for the RIPC stimulus, with the exception that the blood pressure cuff placed on the subject will not be inflated, but the second cuff, that has been placed beside, will be inflated.

Timeline

• Start date: 2008-03-01
• Primary completion: 2012-12-01
• Completion: 2012-12-01
• First posted: 2008-04-01
• Last updated: 2013-08-27

Locations

1 site across 1 country: Canada