CoolCap Trial, Treatment of Perinatal Hypoxic-Ischemic Encephalopathy

Olympic Medical

Status

Completed

Conditions

Neonatal Hypoxic-Ischemic Encephalopathy (HIE)

Treatments

Device: Cool-Cap

Study type

Interventional

Funder types

Industry

Identifiers

NCT00383305

PMA P040025

HIE-0198

IDE G990037

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

1 to 6 hours old

Volunteers

No Healthy Volunteers

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