CoolCap Trial, Treatment of Perinatal Hypoxic-Ischemic Encephalopathy

This study has been completed.
Information provided by:
Olympic Medical Identifier:
First received: September 29, 2006
Last updated: NA
Last verified: September 2006
History: No changes posted

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.

Condition Intervention
Neonatal Hypoxic-Ischemic Encephalopathy (HIE)
Device: Cool-Cap

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Brain-Cooling for the Treatment of Perinatal Hypoxic-Ischemic Encephalopathy

Resource links provided by NLM:

Further study details as provided by Olympic Medical:

Primary Outcome Measures:
  • Combined death or severe neurodevelopmental disability in the first 18 months of life.

Secondary Outcome Measures:
  • Length of hospitalization during NICU course in those surviving to discharge and for whom support was not withdrawn.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)

Estimated Enrollment: 235
Study Start Date: July 1999
Estimated Study Completion Date: September 2003
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.


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

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
  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 identifier: NCT00383305

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

Publications: Identifier: NCT00383305     History of Changes
Other Study ID Numbers: IDE G990037, PMA P040025, HIE-0198
Study First Received: September 29, 2006
Last Updated: September 29, 2006
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
United Kingdom: Department of Health
United States: Institutional Review Board

Keywords provided by Olympic Medical:
birth asphyxia
neonatal encephalopathy
Asphyxia Neonatorum
hypothermia, therapeutic
brain cooling
selective head cooling

Additional relevant MeSH terms:
Brain Diseases
Brain Ischemia
Hypoxia-Ischemia, Brain
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Hypoxia, Brain
Nervous System Diseases
Vascular Diseases processed this record on March 31, 2015