CoolCap Trial, Treatment of Perinatal Hypoxic-Ischemic Encephalopathy

NCT ID: NCT00383305

Last Updated: 2006-10-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

235 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-07-31

Study Completion Date

2003-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Neonatal Hypoxic-Ischemic Encephalopathy (HIE)

Keywords

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neonatal hypoxic ischemic encephalopathy HIE birth asphyxia neonatal encephalopathy Asphyxia Neonatorum hypothermia, therapeutic brain cooling selective head cooling

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Cool-Cap

Intervention Type DEVICE

Eligibility Criteria

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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
Minimum Eligible Age

1 Hour

Maximum Eligible Age

6 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Olympic Medical

INDUSTRY

Sponsor Role lead

Principal Investigators

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Peter D Gluckman, M.D.

Role: PRINCIPAL_INVESTIGATOR

The Liggins Institute, University of Auckland; Auckland, New Zealand

John S. Wyatt, M.D.

Role: PRINCIPAL_INVESTIGATOR

University College London; London, UK

Alistair J Gunn, M.D., Ph.D.

Role: STUDY_DIRECTOR

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

Locations

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Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

Children's Hospital and Research Center at Oakland

Oakland, California, United States

Site Status

University of California San Diego Medical Center (Hillcrest)

San Diego, California, United States

Site Status

University of California San Francisco Children's Hospital

San Francisco, California, United States

Site Status

Children's Hospital of Denver

Denver, Colorado, United States

Site Status

Children's Memorial Hospital / Prentice Women's Hospital

Chicago, Illinois, United States

Site Status

University of Illinois at Chicago Medical Center

Chicago, Illinois, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

University of Michigan Medical Center - Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Children's Hospital and Clinics of Minneapolis

Minneapolis, Minnesota, United States

Site Status

Schneider Children's Hospital

New Hyde Park, New York, United States

Site Status

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

New York, New York, United States

Site Status

Golisano Children's Hospital at Strong

Rochester, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Children's Hospital of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status

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

Philadelphia, Pennsylvania, United States

Site Status

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

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Royal Alexandra Hospital

Edmonton, Alberta, Canada

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Children's Hospital of Eastern Ontario / The Ottawa Hospital

Ottawa, Ontario, Canada

Site Status

University of Auckland - National Women's Hospital

Auckland, , New Zealand

Site Status

Southmead Hospital

Bristol, England, United Kingdom

Site Status

St. Michael's Hospital

Bristol, , United Kingdom

Site Status

Hammersmith Hospital

London, , United Kingdom

Site Status

University College Hospital

London, , United Kingdom

Site Status

Countries

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United States Canada New Zealand United Kingdom

References

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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.

Reference Type RESULT
PMID: 15721471 (View on PubMed)

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.

Reference Type RESULT
PMID: 15885292 (View on PubMed)

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.

Reference Type RESULT
PMID: 15885291 (View on PubMed)

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.

Reference Type RESULT
PMID: 16199715 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27799322 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26283669 (View on PubMed)

Other Identifiers

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PMA P040025

Identifier Type: -

Identifier Source: secondary_id

HIE-0198

Identifier Type: -

Identifier Source: secondary_id

IDE G990037

Identifier Type: -

Identifier Source: org_study_id