Neonatal Hypoxic-Ischemic Encephalopathy (HIE)NCT00383305
CoolCap Trial, Treatment of Perinatal Hypoxic-Ischemic Encephalopathy
A study testing Cool-Cap in people with Neonatal Hypoxic-Ischemic Encephalopathy (HIE), run by Olympic Medical at 27 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 hour to 6 hours
- Conditions the study is for
- Neonatal Hypoxic-Ischemic Encephalopathy (HIE)
- What is being tested?
- Cool-Cap
- Type of treatment
- Medical device
- How many people
- 235 participants
- Where
- 27 sitesin 4 countries
- Study dates
- Jul 1999to Sep 2003
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 hour to 6 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
Show all 12Show fewer
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
27 sites in 4 countries.
27 sites in 4 countries
United States19 sites
University of Michigan Medical Center - Mott Children's Hospital
Ann Arbor, Michigan, 48109
Johns Hopkins University
Baltimore, Maryland, 21287
Children's Memorial Hospital / Prentice Women's Hospital
Chicago, Illinois, 60611
University of Illinois at Chicago Medical Center
Chicago, Illinois, 60612
Children's Hospital of Denver
Denver, Colorado, 80262
Duke University Medical Center
Durham, North Carolina, 27705
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Children's Hospital and Clinics of Minneapolis
Minneapolis, Minnesota, 55404
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Schneider Children's Hospital
New Hyde Park, New York, 11040
Children's Hospital of new York - Presbyterian (Columbia University)
New York, New York, 10032
Children's Hospital and Research Center at Oakland
Oakland, California, 94609
Children's Hospital of Oklahoma
Oklahoma City, Oklahoma, 73190
AI Dupont Children's Hospital at Thomas Jefferson University Medical Center
Philadelphia, Pennsylvania, 19107
Magee Women's Hospital / Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Golisano Children's Hospital at Strong
Rochester, New York, 14642
University of California San Diego Medical Center (Hillcrest)
San Diego, California, 92103
University of California San Francisco Children's Hospital
San Francisco, California, 94110
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, 27157
United Kingdom4 sites
Southmead Hospital
Bristol, England, BS10 5NB
St. Michael's Hospital
Bristol, BS2 8EG
Hammersmith Hospital
London, W12 0NN
University College Hospital
London, WC1E 6JJ
Canada3 sites
Royal Alexandra Hospital
Edmonton, Alberta, T5H 3V9
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
Children's Hospital of Eastern Ontario / The Ottawa Hospital
Ottawa, Ontario, K1H 8L1
New Zealand1 site
University of Auckland - National Women's Hospital
Auckland
About this study
Official title: Brain-Cooling for the Treatment of Perinatal Hypoxic-Ischemic Encephalopathy
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.
Read the 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.
- Being tested
- Cool-Cap
- Keywords
- neonatal, hypoxic, ischemic, encephalopathy, HIE, birth asphyxia, neonatal encephalopathy, Asphyxia Neonatorum, hypothermia, therapeutic, brain cooling, selective head cooling
- Medical subject headings
- Hypoxia, Ischemia, Brain Diseases, Asphyxia Neonatorum, Hypothermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cool-CapDevice
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Epilepsy: recurrent seizures beyond the neonatal period, requiring anticonvulsant therapy at the time of assessment.
Microcephaly: head circumference < (mean - 2SD)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2006 (estimated)
- Study startJul 1999
- Study completionSep 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Neonatal Hypoxic-Ischemic Encephalopathy (HIE)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 235 participants
Sponsor and investigators
- Lead sponsor
- Olympic Medical
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Peter D Gluckman, M.D., Principal investigator, The Liggins Institute, University of Auckland; Auckland, New ZealandJohn S. Wyatt, M.D., Principal investigator, University College London; London, UKAlistair J Gunn, M.D., Ph.D., Study director, Department of Physiology, University of Auckland; Auckland, New Zealand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00383305
- Sponsor's protocol ID
- IDE G990037
- Other IDs
- PMA P040025, HIE-0198
- Status last verified
- Sep 2006
- First submitted
- 29 Sep 2006
- Last updated
- 3 Oct 2006
- Results posted
- No
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.
PubMed 15721471Dutta 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.
PubMed 15885292Bello 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.
PubMed 15885291Rutherford 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.
PubMed 16199715Basu 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.
PubMed 27799322Basu 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.
PubMed 26283669
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain-Cooling for the Treatment of Perinatal Hypoxic-Ischemic Encephalopathy
- ClinicalTrials.gov ID
- NCT00383305
- Acronym / sponsor ID
- IDE G990037
- Keywords
- neonatal, hypoxic, ischemic, encephalopathy, HIE, birth asphyxia, neonatal encephalopathy, Asphyxia Neonatorum
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 235 participants
- Lead sponsor
- Olympic MedicalIndustry (pharma, biotech, devices)
- Study start
- Jul 1999
- Study completion
- Sep 2003
- First posted
- 3 Oct 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 1 hour to 6 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- 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:
- 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:
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cool-Cap | Device | – |
Primary outcome
Combined death or severe neurodevelopmental disability in the first 18 months of life.
7 secondary outcomes
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2006.
- Results publication: PubMed 15721471Gluckman 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.
- Results publication: PubMed 15885292Dutta 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.
- Results publication: PubMed 15885291Bello 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.
- Results publication: PubMed 16199715Rutherford 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.
- Derived from this study: PubMed 27799322Basu 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.
- Derived from this study: PubMed 26283669Basu 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.
Related trials for Neonatal Hypoxic-Ischemic Encephalopathy (HIE)
RecruitingPhase 2
The PROTECT-HIE Pilot Trial
Hypoxic-ischemic Encephalopathy (HIE)
RecruitingPhase 2/3
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RLS-0071 in Newborns With Moderate or Severe Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia
Hypoxic-Ischemic Encephalopathy
Not yet recruiting
Levetiracetam as an Adjuvant Therapy to Hypothermia in Neonatal Asphyxia
Hypoxic Ischemic Encephalopathy of Newborn, Neuro-protection
RecruitingPhase 2
A Dose Escalation Study of Levetiracetam in the Treatment of Neonatal Seizures
Neonatal Seizure, Neonatal Encephalopathy
RecruitingObservational study
Continuous Monitoring of Body Temperature in Neonates During Therapeutic Hypothermia
Therapeutic Hypothermia, Neonatal Hypoxic-Ischemic Encephalopathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter D Gluckman, M.D. principal investigator
The Liggins Institute, University of Auckland; Auckland, New Zealand
John S. Wyatt, M.D. principal investigator
University College London; London, UK
Alistair J Gunn, M.D., Ph.D. study director
Department of Physiology, University of Auckland; Auckland, New Zealand
27 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cool-Cap in people with Neonatal Hypoxic-Ischemic Encephalopathy (HIE), run by Olympic Medical at 27 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Oct 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, United Kingdom, Canada, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Combined death or severe neurodevelopmental disability in the first 18 months of life.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00383305, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2006.