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

NCT02395276 | Unknown DMC

• 1 other identifier: SMC-0616-13
• Study Type: interventional
• Target: 75
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Congenital Heart Defects; Brain Ischemia; Hypoxia Brain; Child; Hypothermia, Induced

Keywords

Congenital Heart Defects; Hypoxic Ischemic Brain Injury; Hypothermia Therapy; Pediatrics

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Short term neuro-developmental outcome

  2 months

• Short term neuro-developmental outcome

  5 yrs

Study Arms (3)

Whole body hypothermia

ACTIVE COMPARATOR

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

Whole body normothermia

PLACEBO COMPARATOR

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

Control

NO INTERVENTION

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.

Interventions

Whole body hypothermia DEVICE

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.

Also known as: ThermoWrap® cover and Alon® Control Unit

Whole body hypothermia; Whole body normothermia

Eligibility Criteria

• Age: 1 Day - 7 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Every child entering the PCICU, age \< 7 years
• The child will enter arm 1 or 2 if he underwent the event described in section 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
• Initiation of hypothermia treatment within 6 hours following the hypoxic ischemic event defined in section 3.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sheba Medical Center: lead

MeSH Terms

Conditions

Heart Defects, Congenital; Brain Ischemia; Hypoxia, Brain; Hypothermia; Hypoxia-Ischemia, Brain

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Temperature Changes

Study Officials

• Omer B Bar Yosef, MD-PhD

  Chain Sheba Medical Ceneter

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Omer Bar Yosef, MD-PhD

CONTACT

972-52-6667344; omer.baryosef@sheba.health.gov.il

Amir Vardi, MD

CONTACT

927-3-5308010; amir.vardi@sheba.health.gov.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Physician

Study Record Dates

• First Submitted: March 17, 2015
• First Posted: March 23, 2015
• Study Start: April 1, 2015
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2020
• Last Updated: March 24, 2015

Record last verified: 2015-03