Clinical and Genomic Responses to Open Heart Surgery

NCT ID: NCT00650507

Last Updated: 2013-08-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-03-31

Study Completion Date

2012-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Ischemia-reperfusion (IR) Injury

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

children cardiac surgery remote ischemic preconditioning SHAM ischemia-reperfusion

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1

Group Type EXPERIMENTAL

Remote ischemic preconditioning (RIPC)

Intervention Type PROCEDURE

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.

2

Group Type ACTIVE_COMPARATOR

SHAM

Intervention Type PROCEDURE

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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.

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

1 Day

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

The Hospital for Sick Children

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Brian McCrindle

Staff Cardiologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Brian W. McCrindle, MD MPH

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Andrew N. Redington, MB

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Brian W. McCrindle

Toronto, Ontario, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Canada

References

Explore related publications, articles, or registry entries linked to this study.

McCrindle BW, Clarizia NA, Khaikin S, Holtby HM, Manlhiot C, Schwartz SM, Caldarone CA, Coles JG, Van Arsdell GS, Scherer SW, Redington AN. Remote ischemic preconditioning in children undergoing cardiac surgery with cardiopulmonary bypass: a single-center double-blinded randomized trial. J Am Heart Assoc. 2014 Jul 28;3(4):e000964. doi: 10.1161/JAHA.114.000964.

Reference Type DERIVED
PMID: 25074698 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

1000011898

Identifier Type: -

Identifier Source: org_study_id