Clinical and Genomic Responses to Open Heart Surgery
August 25, 2013 updated by: Brian McCrindle, The Hospital for Sick Children
Clinical and Genomic Responses to Open Heart Surgery: A Randomized Controlled Trial of the Effects of Remote Ischemic Preconditioning
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
300
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ontario
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Toronto, Ontario, Canada
- Brian W. McCrindle
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 day to 17 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: 1
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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.
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Active Comparator: 2
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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Impact of RIPC on length of hospital stay.
Time Frame: Assessed through post-operative hospitalization.
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Assessed through post-operative hospitalization.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Gene expression patterns associated with effects of RIPC.
Time Frame: Assessed and recorded during the first 24 hours after surgery.
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Assessed and recorded during the first 24 hours after surgery.
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Patterns of baseline gene expression predictive of the clinical and physiologic impact of cardiopulmonary bypass in children (SHAM group only).
Time Frame: Assessed and recorded during the first 24 hours after surgery.
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Assessed and recorded during the first 24 hours after surgery.
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Impact of RIPC on clinical and physiologic markers related to ischemia-reperfusion injury after cardiac surgery in children.
Time Frame: Assessed and recorded serially during the first 48 hours after surgery.
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Assessed and recorded serially during the first 48 hours after surgery.
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Neurodevelopmental Outcomes (Age < 2 years old at surgery)
Time Frame: Follow-up at 12-18 months post-surgery
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Patients less than a two years of age at the time of surgery will return at 12 -18 months postoperative to be assessed using the BSID- III.
During the same visit, parents will complete questionnaires pertaining to their child's behavior and adaptive behavior; the parent version of the Child Behavior Checklist and the parent version of the Vineland Adaptive Behavior Scales - II.
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Follow-up at 12-18 months post-surgery
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Neurodevelopmental Outcomes (Age 2-6 years old at surgery)
Time Frame: Follow-up at 12-18 months post-surgery
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Patients greater than two years of age at the time of surgery will be assessed using the Wechsler Preschool and Primary Scale of Intelligence-Revised, the Peabody Picture Vocabulary Test - IV and the Beery-Buktenica Developmental Test of Visual-Motor Integration, 5th Edition.
Parents will complete questionnaires pertaining to their child's behavior and adaptive behavior; the parent version of the Child Behavior Checklist and the parent version of the Vineland Adaptive Behavior Scales - II.
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Follow-up at 12-18 months post-surgery
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Brian W. McCrindle, MD MPH, The Hospital for Sick Children
- Principal Investigator: Andrew N. Redington, MB, The Hospital for Sick Children
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2008
Primary Completion (Actual)
December 1, 2012
Study Completion (Actual)
December 1, 2012
Study Registration Dates
First Submitted
March 27, 2008
First Submitted That Met QC Criteria
March 27, 2008
First Posted (Estimate)
April 1, 2008
Study Record Updates
Last Update Posted (Estimate)
August 27, 2013
Last Update Submitted That Met QC Criteria
August 25, 2013
Last Verified
August 1, 2013
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1000011898
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.