Neonatal Hypoxic-Ischemic Encephalopathy (HIE) Clinical Trial
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.
| Status | Completed |
| Enrollment | 235 |
| Est. completion date | September 2003 |
| Est. primary completion date | |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | N/A to 6 Hours |
| Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Canada | Royal Alexandra Hospital | Edmonton | Alberta |
| Canada | University of Alberta Hospital | Edmonton | Alberta |
| Canada | Children's Hospital of Eastern Ontario / The Ottawa Hospital | Ottawa | Ontario |
| New Zealand | University of Auckland - National Women's Hospital | Auckland | |
| United Kingdom | Southmead Hospital | Bristol | England |
| United Kingdom | St. Michael's Hospital | Bristol | |
| United Kingdom | Hammersmith Hospital | London | |
| United Kingdom | University College Hospital | London | |
| United States | University of Michigan Medical Center - Mott Children's Hospital | Ann Arbor | Michigan |
| United States | Johns Hopkins University | Baltimore | Maryland |
| United States | Children's Memorial Hospital / Prentice Women's Hospital | Chicago | Illinois |
| United States | University of Illinois at Chicago Medical Center | Chicago | Illinois |
| United States | Children's Hospital of Denver | Denver | Colorado |
| United States | Duke University Medical Center | Durham | North Carolina |
| United States | Arkansas Children's Hospital | Little Rock | Arkansas |
| United States | Children's Hospital and Clinics of Minneapolis | Minneapolis | Minnesota |
| United States | Vanderbilt University Medical Center | Nashville | Tennessee |
| United States | Schneider Children's Hospital | New Hyde Park | New York |
| United States | Children's Hospital of new York - Presbyterian (Columbia University) | New York | New York |
| United States | Children's Hospital and Research Center at Oakland | Oakland | California |
| United States | Children's Hospital of Oklahoma | Oklahoma City | Oklahoma |
| United States | AI Dupont Children's Hospital at Thomas Jefferson University Medical Center | Philadelphia | Pennsylvania |
| United States | Magee Women's Hospital / Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania |
| United States | Golisano Children's Hospital at Strong | Rochester | New York |
| United States | University of California San Diego Medical Center (Hillcrest) | San Diego | California |
| United States | University of California San Francisco Children's Hospital | San Francisco | California |
| United States | Wake Forest University Baptist Medical Center | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Olympic Medical |
United States, Canada, New Zealand, United Kingdom,
Bello SO. Selective head cooling after neonatal encephalopathy. Lancet. 2005 May 7-13;365(9471):1619; author reply 1619-20. — View Citation
Dutta S, Pradeep GC, Narang A. Selective head cooling after neonatal encephalopathy. Lancet. 2005 May 7-13;365(9471):1619; author reply 1619-20. — View Citation
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. 200 — View Citation
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Combined death or severe neurodevelopmental disability in the first 18 months of life. | |||
| Secondary | Length of hospitalization during NICU course in those surviving to discharge and for whom support was not withdrawn. | |||
| Secondary | Multi-organ dysfunction (3 or more organ systems) in the neonatal period. | |||
| Secondary | 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 | |||
| Secondary | Bayley PDI score | |||
| Secondary | Sensorineural hearing loss >= 40 dB | |||
| Secondary | Epilepsy: recurrent seizures beyond the neonatal period, requiring anticonvulsant therapy at the time of assessment. | |||
| Secondary | Microcephaly: head circumference < (mean - 2SD) |