NCT00383305

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
235

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jul 1999

Longer than P75 for not_applicable

Geographic Reach
4 countries

27 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 1999

Completed
4.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2003

Completed
3.1 years until next milestone

First Submitted

Initial submission to the registry

September 29, 2006

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 3, 2006

Completed
Last Updated

October 3, 2006

Status Verified

September 1, 2006

First QC Date

September 29, 2006

Last Update Submit

September 29, 2006

Conditions

Keywords

neonatalhypoxicischemicencephalopathyHIEbirth asphyxianeonatal encephalopathyAsphyxia Neonatorumhypothermia, therapeuticbrain coolingselective head cooling

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (7)

  • Length of hospitalization during NICU course in those surviving to discharge and for whom support was not withdrawn.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

  • +2 more secondary outcomes

Interventions

Cool-CapDEVICE

Eligibility Criteria

Age1 Hour - 6 Hours
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (27)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Children's Hospital and Research Center at Oakland

Oakland, California, 94609, United States

Location

University of California San Diego Medical Center (Hillcrest)

San Diego, California, 92103, United States

Location

University of California San Francisco Children's Hospital

San Francisco, California, 94110, United States

Location

Children's Hospital of Denver

Denver, Colorado, 80262, United States

Location

Children's Memorial Hospital / Prentice Women's Hospital

Chicago, Illinois, 60611, United States

Location

University of Illinois at Chicago Medical Center

Chicago, Illinois, 60612, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

University of Michigan Medical Center - Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Children's Hospital and Clinics of Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

Schneider Children's Hospital

New Hyde Park, New York, 11040, United States

Location

Children's Hospital of new York - Presbyterian (Columbia University)

New York, New York, 10032, United States

Location

Golisano Children's Hospital at Strong

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Children's Hospital of Oklahoma

Oklahoma City, Oklahoma, 73190, United States

Location

AI Dupont Children's Hospital at Thomas Jefferson University Medical Center

Philadelphia, Pennsylvania, 19107, United States

Location

Magee Women's Hospital / Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Children's Hospital of Eastern Ontario / The Ottawa Hospital

Ottawa, Ontario, K1H 8L1, Canada

Location

University of Auckland - National Women's Hospital

Auckland, New Zealand

Location

Southmead Hospital

Bristol, England, BS10 5NB, United Kingdom

Location

St. Michael's Hospital

Bristol, BS2 8EG, United Kingdom

Location

Hammersmith Hospital

London, W12 0NN, United Kingdom

Location

University College Hospital

London, WC1E 6JJ, United Kingdom

Location

Related Publications (6)

  • Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005 Feb 19-25;365(9460):663-70. doi: 10.1016/S0140-6736(05)17946-X.

  • Dutta S, Pradeep GC, Narang A. Selective head cooling after neonatal encephalopathy. Lancet. 2005 May 7-13;365(9471):1619; author reply 1619-20. doi: 10.1016/S0140-6736(05)66503-8. No abstract available.

  • Bello SO. Selective head cooling after neonatal encephalopathy. Lancet. 2005 May 7-13;365(9471):1619; author reply 1619-20. doi: 10.1016/S0140-6736(05)66504-X. No abstract available.

  • Rutherford MA, Azzopardi D, Whitelaw A, Cowan F, Renowden S, Edwards AD, Thoresen M. Mild hypothermia and the distribution of cerebral lesions in neonates with hypoxic-ischemic encephalopathy. Pediatrics. 2005 Oct;116(4):1001-6. doi: 10.1542/peds.2005-0328.

  • Basu SK, Salemi JL, Gunn AJ, Kaiser JR; CoolCap Study Group. Hyperglycaemia in infants with hypoxic-ischaemic encephalopathy is associated with improved outcomes after therapeutic hypothermia: a post hoc analysis of the CoolCap Study. Arch Dis Child Fetal Neonatal Ed. 2017 Jul;102(4):F299-F306. doi: 10.1136/archdischild-2016-311385. Epub 2016 Oct 31.

  • Basu SK, Kaiser JR, Guffey D, Minard CG, Guillet R, Gunn AJ; CoolCap Study Group. Hypoglycaemia and hyperglycaemia are associated with unfavourable outcome in infants with hypoxic ischaemic encephalopathy: a post hoc analysis of the CoolCap Study. Arch Dis Child Fetal Neonatal Ed. 2016 Mar;101(2):F149-55. doi: 10.1136/archdischild-2015-308733. Epub 2015 Aug 17.

MeSH Terms

Conditions

HypoxiaIschemiaBrain DiseasesAsphyxia NeonatorumHypothermia

Condition Hierarchy (Ancestors)

Signs and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and SymptomsPathologic ProcessesCentral Nervous System DiseasesNervous System DiseasesInfant, Newborn, DiseasesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesBody Temperature Changes

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR
  • Alistair J Gunn, M.D., Ph.D.

    Department of Physiology, University of Auckland; Auckland, New Zealand

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

September 29, 2006

First Posted

October 3, 2006

Study Start

July 1, 1999

Study Completion

September 1, 2003

Last Updated

October 3, 2006

Record last verified: 2006-09

Locations