CoolCap Trial, Treatment of Perinatal Hypoxic-Ischemic Encephalopathy

September 29, 2006 updated by: Olympic Medical

Brain-Cooling for the Treatment of Perinatal Hypoxic-Ischemic Encephalopathy

This is a research study of head cooling. Its goal is to determine whether cooling babies' heads can reduce or prevent brain damage that may have resulted from temporarily reduced oxygen supply to the brain. In this study, half of the babies (selected at random) will have a special cooling cap with circulating water placed on their head for 72 hours to lower the temperature of their brain. The rest of the baby's body will be maintained at a defined temperature by a standard overhead radiant heater. The study protocol includes the taking and analysis of blood samples, performance of brain wave tests, imaging of the brain by ultrasound, and other tests as clinically indicated. Neurodevelopmental outcome will also be assessed at 18 months of age.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The objective of this study is to determine whether head cooling with mild systemic hypothermia in term infants following perinatal asphyxia is a safe procedure that improves survival without neurodevelopmental disability. Outcome will be assessed by survival and neurological and neurodevelopmental testing at 18 months of age.

Within 6 hours of birth, infants will be randomized to either a non-cooled control group with rectal temperature kept at 37+/-0.5 degC or to head cooling with mild systemic hypothermia as follows. A cooling device capable of circulating cool water in a temperature-regulated manner through a cap fitted around the infant's scalp will cool the head. The core rectal temperature of the infant will be maintained at 34.5+/-0.5 degC by adjusting the cap water temperature. The infant's rectal, nasopharyngeal, scalp (fontanel), and skin (abdominal) temperatures will be continuously monitored. Also, metabolic, cardiovascular, pulmonary and coagulation laboratory measurements will be assessed at predefined time points. Cooling will be maintained for 72 hours, followed by four hours of rewarming, with the goal of raising the rectal temperature to normal body temperature by 0.5 degC per hour. The outcome measure of severe neurodevelopmental disability and survival rates at 18 months of age will be assessed by blinded, independent observers.

Study Type

Interventional

Enrollment

235

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2B7
        • University of Alberta Hospital
      • Edmonton, Alberta, Canada, T5H 3V9
        • Royal Alexandra Hospital
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L1
        • Children's Hospital of Eastern Ontario / The Ottawa Hospital
  • New Zealand
      • Auckland, New Zealand
        • University of Auckland - National Women's Hospital
  • United Kingdom
      • Bristol, United Kingdom, BS2 8EG
        • St. Michael's Hospital
      • London, United Kingdom, W12 0NN
        • Hammersmith Hospital
      • London, United Kingdom, WC1E 6JJ
        • University College Hospital
    • England
      • Bristol, England, United Kingdom, BS10 5NB
        • Southmead Hospital
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Arkansas Children's Hospital
    • California
      • Oakland, California, United States, 94609
        • Children's Hospital and Research Center at Oakland
      • San Diego, California, United States, 92103
        • University of California San Diego Medical Center (Hillcrest)
      • San Francisco, California, United States, 94110
        • University of California San Francisco Children's Hospital
    • Colorado
      • Denver, Colorado, United States, 80262
        • Children's Hospital of Denver
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago Medical Center
      • Chicago, Illinois, United States, 60611
        • Children's Memorial Hospital / Prentice Women's Hospital
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Medical Center - Mott Children's Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospital and Clinics of Minneapolis
    • New York
      • New Hyde Park, New York, United States, 11040
        • Schneider Children's Hospital
      • New York, New York, United States, 10032
        • Children's Hospital of new York - Presbyterian (Columbia University)
      • Rochester, New York, United States, 14642
        • Golisano Children's Hospital at Strong
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Baptist Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73190
        • Children's Hospital of Oklahoma
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • AI Dupont Children's Hospital at Thomas Jefferson University Medical Center
      • Pittsburgh, Pennsylvania, United States, 15213
        • Magee Women's Hospital / Children's Hospital of Pittsburgh
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 hour to 6 hours (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Infants are assessed sequentially by criteria A, B and C listed below. Infant must meet all three criteria to be eligible for trial enrollment.

  • Criteria A: Infants >= 36 weeks gestation admitted to the NICU with ONE of the following:

    • Apgar score of <= 5 at 10 minutes after birth;
    • Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth;
    • Acidosis defined as either umbilical cord pH or any arterial pH within 60 minutes of birth < 7.00; or
    • Base Deficit <= -16 mmol/L in umbilical cord blood sample OR any blood sample within 60 minutes of birth (arterial or venous blood).

  • Criteria B: Moderate to severe encephalopathy consisting of altered state of consciousness (as shown by lethargy, stupor, or coma) AND at least one or more of the following:

    • Hypotonia;
    • Abnormal reflexes, including oculomotor or pupillary abnormalities;
    • An absent or weak suck;
    • Clinical seizures
  • Criteria C: At least 20 minutes duration of amplitude integrated EEG (aEEG/CFM) recording that shows abnormal background aEEG/CFM activity or seizures. The aEEG/CFM is to be performed from one hour of age. If subsequently an abnormal aEEG/CFM is recorded before 5.5 hours of age, the infant is then eligible for enrollment. The aEEG is not to be performed within 30 minutes of IV anticonvulsant therapy as this may cause suppression of EEG activity. In particular, high dose prophylactic anticonvulsant therapy (e.g., >20 mg/kg phenobarbitone) is not to be given prior to performing the aEEG/CFM.

Exclusion Criteria:

  • Infant expected to be > 5.5 hours of age at the time of randomization
  • Prophylactic administration of high dose anticonvulsants (e.g., >20 mg/kg phenobarbitone). After trial entry phenobarbitone or other anticonvulsant therapy is allowed to be given as clinically indicated to treat seizures.
  • Major congenital abnormalities, such as diaphragmatic hernia requiring ventilation, or congenital abnormalities suggestive of chromosomal anomaly or other syndromes that include brain dysgenesis
  • Imperforate anus
  • Evidence of head trauma or skull fracture causing major intracranial hemorrhage
  • Infant < 1,800 g birth weight
  • Head circumference < (mean - 2SD) for gestation if birth weight and length are > (mean - 2SD)
  • Infant "in extremis" (i.e. an infant for whom no other additional intensive management would be offered in the judgment of the attending neonatologist)
  • Unavailability of essential equipment (e.g., Cool-Cap, aEEG/CFM)
  • Planned concurrent participation in other experimental treatments

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Combined death or severe neurodevelopmental disability in the first 18 months of life.

Secondary Outcome Measures

Outcome Measure
Length of hospitalization during NICU course in those surviving to discharge and for whom support was not withdrawn.
Multi-organ dysfunction (3 or more organ systems) in the neonatal period.
Rate of multiple handicap in survivors (Multiple handicap will be defined as the presence of any two of the following in an infant: neuromotor disability (Level 3-5 on GMF classification), mental delay, epilepsy, cortical visual impairment, sensorineural
Bayley PDI score
Sensorineural hearing loss >= 40 dB
Epilepsy: recurrent seizures beyond the neonatal period, requiring anticonvulsant therapy at the time of assessment.
Microcephaly: head circumference < (mean - 2SD)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Olympic Medical

Investigators

  • Principal Investigator: Peter D Gluckman, M.D., The Liggins Institute, University of Auckland; Auckland, New Zealand
  • Principal Investigator: John S. Wyatt, M.D., University College London; London, UK
  • Study Director: Alistair J Gunn, M.D., Ph.D., Department of Physiology, University of Auckland; Auckland, New Zealand

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 1999

Study Completion

September 1, 2003

Study Registration Dates

First Submitted

September 29, 2006

First Submitted That Met QC Criteria

September 29, 2006

First Posted (Estimate)

October 3, 2006

Study Record Updates

Last Update Posted (Estimate)

October 3, 2006

Last Update Submitted That Met QC Criteria

September 29, 2006

Last Verified

September 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IDE G990037
  • PMA P040025
  • HIE-0198

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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