Pediatric Remote Ischemic Pre-conditioning Prior to Complex Cardiac Surgery (PREP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Alberta
Sponsor:
Collaborator:
Women and Children's Health Research Institute, Canada
Information provided by (Responsible Party):
Gonzalo Garcia Guerra, University of Alberta
ClinicalTrials.gov Identifier:
NCT01739088
First received: November 27, 2012
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

In 2012, infants having surgery for congenital heart disease have a high survival. The investigators are now focused on improving how sick these infants become after surgery (short term outcomes) and their later neurodevelopment (long term outcomes). During heart surgery, cardiopulmonary bypass (CPB; the heart-lung machine) takes over heart function while the surgeon repairs the heart disease. During this surgery there are periods of time when the amount of blood going to the heart and brain is lower than usual, called "ischemia". Once the surgery is finished the blood going to the heart and brain is increased to normal again, called "reperfusion". This ischemia-reperfusion can cause injury to the heart, brain, and other organs, affecting the short and long term outcomes in these infants. Adult studies have shown that a short time of ischemia to the legs for 5-10 minutes [the legs are not damaged by a short time of ischemia, unlike the heart or brain], before severe ischemia to another distant vulnerable vital organ [like the heart or brain], can protect this other vital organ from ischemia-reperfusion injury. This is called "remote ischemic preconditioning" (RIPC). Our objective is to test whether RIPC before heart surgery can improve the recovery of the heart and brain after heart surgery in newborn babies with congenital heart disease. The investigators will test whether RIPC will result in lower peak lactate and troponin levels on the day after heart surgery. Lactate levels are a marker for how much the different tissues of the body suffer from ischemia-reperfusion injury. Troponin is released from damaged heart during ischemia-reperfusion. In our trial infants will be randomized to RIPC or control. This means each baby has an equal chance of being in one group or the other. The intervention group will have RIPC before surgery; the "control group" will not. The investigators hope this trial will lead to a larger study to test if RIPC results in fewer days on a breathing machine after surgery, lower mortality, and higher scores on neurodevelopmental tests at 2 years of age.


Condition Intervention
Congenital Heart Disease
Ischemia-reperfusion Injury
Other: Remote ischemic pre-conditioning stimulus.
Other: Sham Ischemic Pre-conditioning

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Pediatric Remote Ischemic Pre-conditioning Prior to Complex Cardiac Surgery

Resource links provided by NLM:


Further study details as provided by University of Alberta:

Primary Outcome Measures:
  • To demonstrate the feasibility of patient recruitment to a remote ischemic pre-conditioning randomized controlled trial at our center [ Time Frame: One year ] [ Designated as safety issue: No ]
    This is a pilot study looking at feasibility to conduct a larger randomized controlled study on pediatric remote ischemic pre-conditioning at our center.


Secondary Outcome Measures:
  • Troponin I levels [ Time Frame: One year ] [ Designated as safety issue: No ]
    We will obtain blood samples for troponin I levels pre-Cardiopulmonary bypass, 3, 6, 12 and 24 hours after the surgery. Troponin I levels, as a marker of myocardial ischemia, have been used in previous adult and pediatric studies on preconditioning.

  • Highest inotropic score during the first 24 hours after cardiac surgery [ Time Frame: 24 hours after the surgery ] [ Designated as safety issue: No ]

    Inotrope score is a useful predictor of morbidity and mortality in children who undergo heart surgery.

    The inotropic score is calculated as follows: 1 point is assigned for each mcg/kg/min of dopamine and dobutamine, and 10 points is assigned for each 0.1 mcg/kg/min of epinephrine, norepinephrine, and phenylephrine. Inotrope score is a useful predictor of morbidity and mortality in children who undergo heart surgery.


  • Mechanical ventilation days [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Number of days the patient remains on mechanical ventilation after the surgical repair.

  • Mortality at 30 days [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Proportion of patients who dies within 30 days of their surgical repair

  • Intensive care unit length of stay [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Number of days the patient remains in the pediatric intensive care unit after the surgical repair

  • Neurodevelopmental outcome [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The Bayley Scales of Infant and Toddler Development (bayley III) will be used to evaluate the long term outcome of the study subjects. Bayley III is a widely accepted standardized outcome measure used in neonatal follow-up clinics is part of the assessment routinely performed in these patients by the Pediatric Complex Therapies Program.Five certified pediatric psychologist (blinded to treatment allocation) will assess the neurodevelopmental outcomes at the tertiary site of origin.

  • Highest arterial lactate level during the first 24 hours after surgical repair for congenital heart disease. [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Peak lactate levels during the first 24 hours after surgical repair for congenital heart disease it has consistently shown to be associated with neurodevelopmental outcomes in the long term. Arterial blood lactate levels are obtained every 2 hours as a standard of care.


Estimated Enrollment: 50
Study Start Date: March 2013
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Remote ischemic preconditioning stimulus
The remote ischemic pre-conditioning arm of the study is the experimental one. Patients in this arm will receive a remote ischemic pre-conditioning stimulus at 24-48 hours pre-operatively, and again intra-operatively before CPB.
Other: Remote ischemic pre-conditioning stimulus.
Forty eight to 24 hours prior to the surgery, patient assigned to remote ischemic pre-conditioning stimulus (RIPC) will have blood pressure cuffs placed on both lower limbs around the upper thigh, and will then have the cuff inflated around the lower limb to a pressure 10 mmHg above systolic blood pressure for 5 minutes, followed by 5 minutes of cuff deflation. This will be done sequentially on each lower limb for two cycles on each limb. In the operating room, after induction of anesthesia, the exact same procedure will be performed in the RIPC group. For each intervention, the legs will be covered by a drape, so that whether the cuff is being inflated around the leg or underneath the leg is not seen by any member of the health care team.
Sham Comparator: Sham Ischemic Pre-conditioning
In the control (sham-RIPC) group the cuff will be placed just underneath the upper thigh and the cuff will be inflated for 5 minutes, followed by 5 minutes of cuff deflation, done sequentially for two cycles on each side. In the operating room, after induction of anesthesia, the exact same procedure will be performed in the the control group.
Other: Sham Ischemic Pre-conditioning
In the control (sham Ischemic Pre-conditioning) group 48 to 24 hours prior to the surgery a cuff will be placed just underneath the upper thigh and the cuff will be inflated for 5 minutes, followed by 5 minutes of cuff deflation, done sequentially for two cycles on each side.In the operating room, after induction of anesthesia, the exact same procedure will be performed in the RIPC group.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 6 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Admitted to the Stollery Children's Hospital Neonatal, Cardiology Unit or Pediatric Intensive Care Unit pre-operative for planned surgical repair of congenital heart disease with cardiopulmonary bypass and aortic cross-clamp
  • Age at surgery <6 weeks old
  • Parental consent for enrolment

Exclusion Criteria:

  • Cardio Pulmonary Resuscitation (CPR), Extra-corporeal life support, ECG confirmed myocardial infarction, known chromosomal abnormalities, or known abnormal brain ultrasound (with signs of brain malformation, stroke, or intracranial bleed) pre-operatively
  • Gestational age < 37 weeks
  • Known medications that prevent RIPC within 48 hours of surgery, including, naloxone, sulphonylurea hypoglycemic agent, angiotensin receptor blocker, or beta blocker
  • Patients not admitted to the Neonatal Intensive Care Unit, Pediatric Intensive Care Unit or Pediatric Cardiology Unit 24 hours before surgery. A brain ultrasound, ECG, and chromosomal analysis are done pre-operatively as a standard of care in our institution
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01739088

Contacts
Contact: Gonzalo Garcia Guerra, MD, MSc 780-407-6033 Gonzalo.Guerra@albertahealthservices.ca
Contact: Ari Joffe, MD 780-407-6033 Ari.Joffe@albertahealthservices.ca

Locations
Canada, Alberta
Stollery Children's Hospital Recruiting
Edmonton, Alberta, Canada, T6G2B3
Principal Investigator: Gonzalo Garcia Guerra, MD, MSc         
Sub-Investigator: Ari Joffe, MD         
Sub-Investigator: Charlene Robertson, MD         
Sub-Investigator: David Ross, MD         
Sub-Investigator: Ivan Rebeyka, MD         
Sub-Investigator: Jon Duff, MD         
Sub-Investigator: Rob Seal, MD         
Sub-Investigator: Ernest Phillipos, MD         
Sub-Investigator: Irina Dinu, PhD         
Sub-Investigator: Bryan Acton, MD         
Sub-Investigator: Cathy Sheppard, RN         
Sub-Investigator: Gwen Alton, RN         
Sub-Investigator: Coleen Gresiuk, RN         
Sponsors and Collaborators
University of Alberta
Women and Children's Health Research Institute, Canada
Investigators
Principal Investigator: Gonzalo Garcia Guerra, MD, MSc University of Alberta
Study Chair: Ari Joffe, MD University of Alberta
  More Information

No publications provided

Responsible Party: Gonzalo Garcia Guerra, Clinical Assistant Professor, University of Alberta
ClinicalTrials.gov Identifier: NCT01739088     History of Changes
Other Study ID Numbers: Pro00032388
Study First Received: November 27, 2012
Last Updated: June 2, 2014
Health Authority: Canada: Ethics Review Committee

Keywords provided by University of Alberta:
Congenital heart disease
pediatrics
ischemia-reperfusion injury
long term outcomes

Additional relevant MeSH terms:
Ischemia
Heart Diseases
Heart Defects, Congenital
Reperfusion Injury
Pathologic Processes
Cardiovascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities
Vascular Diseases
Postoperative Complications

ClinicalTrials.gov processed this record on September 16, 2014