Clinical and Genomic Responses to Open Heart Surgery

NCT00650507 | Completed Phase 3

• 1 other identifier: 1000011898
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ischemia-reperfusion (IR) Injury

Keywords

children; cardiac surgery; remote ischemic preconditioning; SHAM; ischemia-reperfusion

Outcome Measures

Primary Outcomes (1)

• Impact of RIPC on length of hospital stay.

  Assessed through post-operative hospitalization.

Secondary Outcomes (5)

• Gene expression patterns associated with effects of RIPC.

  Assessed and recorded during the first 24 hours after 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

• Neurodevelopmental Outcomes (Age 2-6 years old at surgery)

  Follow-up at 12-18 months post-surgery

Study Arms (2)

1

EXPERIMENTAL

Procedure: Remote ischemic preconditioning (RIPC)

2

ACTIVE COMPARATOR

Procedure: SHAM

Interventions

Remote ischemic preconditioning (RIPC) 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.

1

SHAM 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.

2

Eligibility Criteria

• Age: 1 Day - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Hospital for Sick Children: lead

Study Sites (1)

Brian W. McCrindle

Toronto, Ontario, Canada

Location

Related Publications (1)

• 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.

  PMID: 25074698 DERIVED

MeSH Terms

Conditions

Wounds and Injuries

Interventions

salicylhydroxamic acid

Study Officials

• Brian W. McCrindle, MD MPH

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Andrew N. Redington, MB

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Cardiologist

Study Record Dates

• First Submitted: March 27, 2008
• First Posted: April 1, 2008
• Study Start: March 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 27, 2013

Record last verified: 2013-08

Locations

CA (1)