CoolCap Trial, Treatment of Perinatal Hypoxic-Ischemic Encephalopathy

Brain-Cooling for the Treatment of Perinatal Hypoxic-Ischemic Encephalopathy

Sponsors

Lead Sponsor: Olympic Medical

Source Olympic Medical
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.

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.

Overall Status Completed
Start Date July 1999
Completion Date September 2003
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Combined death or severe neurodevelopmental disability in the first 18 months of life.
Secondary Outcome
Measure Time Frame
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)
Enrollment 235
Condition
Intervention

Intervention Type: Device

Intervention Name: Cool-Cap

Eligibility

Criteria:

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

Gender: All

Minimum Age: N/A

Maximum Age: 6 Hours

Healthy Volunteers: No

Overall Official
Location
Facility:
Arkansas Children's Hospital | Little Rock, Arkansas, 72202, United States
Children's Hospital and Research Center at Oakland | Oakland, California, 94609, United States
University of California San Diego Medical Center (Hillcrest) | San Diego, California, 92103, United States
University of California San Francisco Children's Hospital | San Francisco, California, 94110, United States
Children's Hospital of Denver | Denver, Colorado, 80262, United States
Children's Memorial Hospital / Prentice Women's Hospital | Chicago, Illinois, 60611, United States
University of Illinois at Chicago Medical Center | Chicago, Illinois, 60612, United States
Johns Hopkins University | Baltimore, Maryland, 21287, United States
University of Michigan Medical Center - Mott Children's Hospital | Ann Arbor, Michigan, 48109, United States
Children's Hospital and Clinics of Minneapolis | Minneapolis, Minnesota, 55404, United States
Schneider Children's Hospital | New Hyde Park, New York, 11040, United States
Children's Hospital of new York - Presbyterian (Columbia University) | New York, New York, 10032, United States
Golisano Children's Hospital at Strong | Rochester, New York, 14642, United States
Duke University Medical Center | Durham, North Carolina, 27705, United States
Wake Forest University Baptist Medical Center | Winston-Salem, North Carolina, 27157, United States
Children's Hospital of Oklahoma | Oklahoma City, Oklahoma, 73190, United States
AI Dupont Children's Hospital at Thomas Jefferson University Medical Center | Philadelphia, Pennsylvania, 19107, United States
Magee Women's Hospital / Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania, 15213, United States
Vanderbilt University Medical Center | Nashville, Tennessee, 37232, United States
Royal Alexandra Hospital | Edmonton, Alberta, T5H 3V9, Canada
University of Alberta Hospital | Edmonton, Alberta, T6G 2B7, Canada
Children's Hospital of Eastern Ontario / The Ottawa Hospital | Ottawa, Ontario, K1H 8L1, Canada
University of Auckland - National Women's Hospital | Auckland, New Zealand
Southmead Hospital | Bristol, England, BS10 5NB, United Kingdom
St. Michael's Hospital | Bristol, BS2 8EG, United Kingdom
Hammersmith Hospital | London, W12 0NN, United Kingdom
University College Hospital | London, WC1E 6JJ, United Kingdom
Location Countries

Canada

New Zealand

United Kingdom

United States

Verification Date

September 2006

Keywords
Condition Browse
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov