Hypothermia Therapy in Pediatric Cardiac Intensive Care Unit for Suspected for Brain Injury (Coolheart)

Efficacy of Hypothermia Therapy in Pediatric Cardiac Intensive Care Unit in Children Suspected for Brain Injury

Cardiac pathology is a major risk for brain injury and neurodevelopmental deficit. The most common cause of cardiac pathology is congenital heart defects (CHD) about 4-8/1000 live births a year. The most common etiology of the brain insult is hypoxic ischemic injury (HII) as result of hemodynamic instability in the perioperative period. Similar insults in adults with cardiac arrest or infants with neonatal asphyxia, was successfully treated with hypothermia, initiated within 6 hours after the event. Although, hypothermia is most likely an effective treatment for HII in children with cardiac anomaly, it also carries a risk for bleeding or infection of the surgical wound. In this randomized control trial, hypothermia treatment will be compared to normothermia treatment of patients in the pediatric cardiac intensive care unit (PCICU) following severe HII in the PCICU or operating room. The effect will be quantified by MRI, serum biomarkers of brain injury, amplitude integrated EEG, neurological evaluation coagulation and infection evaluation in the acute phase and by developmental assessment at 1, 6 months and 2, 5 years. Favorable effect of hypothermia with minimal risks may open the door for the implementation of hypothermia as a standard care in PCICUs.

Study Overview

• Status: Unknown
• Conditions: Brain Ischemia; Child; Congenital Heart Defects; Hypothermia, Induced; Hypoxia Brain
• Intervention / Treatment: Device: Whole body hypothermia

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Omer Bar Yosef, MD-PhD; Phone Number: 972-52-6667344; Email: omer.baryosef@sheba.health.gov.il
• Study Contact Backup: Name: Amir Vardi, MD; Phone Number: 927-3-5308010; Email: amir.vardi@sheba.health.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 7 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Every child entering the PCICU, age < 7 years
2. The child will enter arm 1 or 2 if he underwent the event described in section 3.

3. Hypoxic ischemic event that would render hypothermia treatment is defined as

   • During the hospitalization in the PCICU before or after the surgery:

   Resuscitation comprised of chest compressions for more than 2 minutes, and the first blood tests immediately after the resuscitation show a serum lactate level of more than 90 mg/dl OR Resuscitation comprised of chest compressions for more than 2 minutes, and the first blood tests immediately after the resuscitation shows a serum lactate level of more than 40 mg/dl and a blood pH level of less than 7.1

   • During the surgery Near infra red spectroscopy lower than 40 for more than 5 minutes AND Serum lactate levels of more than 90 mg/dl during the event OR The patient is re-connected to cardio-pulmonary bypass machine as a result of the event
4. Initiation of hypothermia treatment within 6 hours following the hypoxic ischemic event defined in section 3.

Exclusion criteria

• Suspected hypoxic ischemic event as described in the Inclusion Criteria in the 2 weeks prior to the PCICU admission
• Prolonged low cerebral perfusion before the PCICU admission, with 3 repeated tests in 1 hour of lactate level higher than 40 mg/dl and pH lower than 7.1
• Rejection criteria
• A second resuscitation after the hypoxic ischemic event and before a brain MRI is done

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Whole body hypothermia; Children that had an event suspected for hypoxic ischemic brain injury, according to the inclusion criteria, will be randomly allocated for whole body hypothermia therapy. Treatment will be initiated within 6 hours of the event, the child will be dressed with a cooling suit and their temperature will be monitored. Whole body hypothermia will be to 33 +/- 1 °C . Treatment period will be 48 hours with 24 hours warming up period.	Device: Whole body hypothermia; Treatment will be initiated within 6 hours of the event, the child will be dressed with a cooling suit and their temperature will be monitored. Cooling will be to 33 +/- 1 °C . Treatment period will be 48 hours with 24 hours warming up period.; Other Names: ThermoWrap® cover and Alon® Control Unit
Placebo Comparator: Whole body normothermia; Children that had an event suspected for hypoxic ischemic brain injury, according to the inclusion criteria, will be randomly allocated for normothermia therapy. Treatment will be initiated within 6 hours of the event, the child will be dressed with a cooling suit and their temperature will be monitored. Cooling will be to 36-37 °C . Treatment period will be 72 hrs.	Device: Whole body hypothermia; Treatment will be initiated within 6 hours of the event, the child will be dressed with a cooling suit and their temperature will be monitored. Cooling will be to 33 +/- 1 °C . Treatment period will be 48 hours with 24 hours warming up period.; Other Names: ThermoWrap® cover and Alon® Control Unit
No Intervention: Control; A group of children that underwent a cardiac surgery and was not suspected to have an hypoxic ischemic brain injury. This group will be undergo the similar biomarkers collection as arm 1 and 2. The information will be used to measure the change in biomarkers between surgeries with no HII to those in arm 1+2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers	Each child will have 4 blood samples for biomarkers including S100B, Glial Fibrillary Acidic Protein and Specific Neuronal Enolase at the following schedule: before the cardiac surgery, within 6 hr after the surgery, 24 and 48 hrs after the surgery	48 hours after the surgery
Magnetic Resonance Imaging	In arms 1 and 2 an MRI with the sequences of T1, T2, Diffusion Weighted Imaging, Diffuse Tensor Imaging and Magnetic Resonance Spectroscopy	10 days after
Neurological Evaluation	Neurological assessment will be done prior to the cardiac surgery and and one week (or earlier if the child will be fully recovered and discharged before) using standard neurological evaluation, pediatric stroke outcome measure	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short term neuro-developmental outcome	Neurological assessment using standard neurological evaluation, pediatric stroke outcome measure and pediatric cerebral performance category	2 months
Short term neuro-developmental outcome	At 2 and 5 yrs after the hypothermia treatment a c. Vineland adaptive behavior scale (Vineland™-II) will be done	5 yrs

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Investigators: Principal Investigator: Omer B Bar Yosef, MD-PhD, Chain Sheba Medical Ceneter

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Anticipated): April 1, 2017
• Study Completion (Anticipated): April 1, 2020

Study Registration Dates

• First Submitted: March 17, 2015
• First Submitted That Met QC Criteria: March 20, 2015
• First Posted (Estimate): March 23, 2015

Study Record Updates

• Last Update Posted (Estimate): March 24, 2015
• Last Update Submitted That Met QC Criteria: March 21, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Pediatrics; Congenital Heart Defects; Hypoxic Ischemic Brain Injury; Hypothermia Therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Congenital Abnormalities; Craniocerebral Trauma; Trauma, Nervous System; Signs and Symptoms, Respiratory; Cardiovascular Abnormalities; Body Temperature Changes; Brain Ischemia; Ischemia; Brain Injuries; Heart Defects, Congenital; Hypoxia; Hypothermia
• Other Study ID Numbers: SMC-0616-13