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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00383305




Registration number
NCT00383305
Ethics application status
Date submitted
29/09/2006
Date registered
3/10/2006
Date last updated
3/10/2006

Titles & IDs
Public title
CoolCap Trial, Treatment of Perinatal Hypoxic-Ischemic Encephalopathy
Scientific title
Brain-Cooling for the Treatment of Perinatal Hypoxic-Ischemic Encephalopathy
Secondary ID [1] 0 0
PMA P040025
Secondary ID [2] 0 0
IDE G990037
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neonatal Hypoxic-Ischemic Encephalopathy (HIE) 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Neurological 0 0 0 0
Other neurological disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Combined death or severe neurodevelopmental disability in the first 18 months of life.
Timepoint [1] 0 0
Secondary outcome [1] 0 0
Length of hospitalization during NICU course in those surviving to discharge and for whom support was not withdrawn.
Timepoint [1] 0 0
Secondary outcome [2] 0 0
Multi-organ dysfunction (3 or more organ systems) in the neonatal period.
Timepoint [2] 0 0
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Secondary outcome [4] 0 0
Bayley PDI score
Timepoint [4] 0 0
Secondary outcome [5] 0 0
Sensorineural hearing loss >= 40 dB
Timepoint [5] 0 0
Secondary outcome [6] 0 0
Epilepsy: recurrent seizures beyond the neonatal period, requiring anticonvulsant therapy at the time of assessment.
Timepoint [6] 0 0
Secondary outcome [7] 0 0
Microcephaly: head circumference < (mean - 2SD)
Timepoint [7] 0 0

Eligibility
Key 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.
Minimum age
1 Hour
Maximum age
6 Hours
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
NA
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/1999
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Oklahoma
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
Canada
State/province [13] 0 0
Alberta
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
New Zealand
State/province [15] 0 0
Auckland
Country [16] 0 0
United Kingdom
State/province [16] 0 0
England
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Bristol
Country [18] 0 0
United Kingdom
State/province [18] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Olympic Medical
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT00383305
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Peter D Gluckman, M.D.
Address 0 0
The Liggins Institute, University of Auckland; Auckland, New Zealand
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00383305