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CoolCap Trial, Treatment of Perinatal Hypoxic-Ischemic Encephalopathy

This study has been completed.
Sponsor:
Information provided by:
Olympic Medical
ClinicalTrials.gov Identifier:
NCT00383305
First received: September 29, 2006
Last updated: NA
Last verified: September 2006
History: No changes posted
  Purpose

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  • Length of hospitalization during NICU course in those surviving to discharge and for whom support was not withdrawn.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

  Eligibility

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

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 ClinicalTrials.gov identifier: NCT00383305

  Show 27 Study Locations
Sponsors and Collaborators
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
  More Information

Publications:
ClinicalTrials.gov 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:
neonatal
hypoxic
ischemic
encephalopathy
HIE
birth asphyxia
neonatal encephalopathy
Asphyxia Neonatorum
hypothermia, therapeutic
brain cooling
selective head cooling

Additional relevant MeSH terms:
Brain Diseases
Brain Ischemia
Hypoxia-Ischemia, Brain
Ischemia
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Hypoxia, Brain
Nervous System Diseases
Pathologic Processes
Vascular Diseases

ClinicalTrials.gov processed this record on November 27, 2014