Moderate Hypothermia in Neonatal Hypoxic Ischemic Encephalopathy

NCT ID: NCT02826941

Last Updated: 2016-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-06-30
• Study Completion Date: 2004-06-30

Brief Summary

This study was a multicenter, randomized, controlled pilot trial of moderate systemic hypothermia (33°C) vs normothermia (37°C) for 48 hours in infants with neonatal encephalopathy instituted within 6 hours of birth or hypoxic-ischemic event.

Detailed Description

The trial tested the ability to initiate systemic hypothermia in outlying hospitals and participating tertiary care centers, and determined the incidence of adverse neurologic outcomes of death and developmental scores at 12 months by Bayley II or Vineland tests between normothermic and hypothermic groups. This trial identified potential safety outcomes, compared the adverse effects of hypothermia among hypoxic-ischemic encephalopathy (HIE) infants in the normothermic and hypothermic treatment groups, and obtained rates of adverse outcomes.

Conditions

Neonatal Asphyxial Encephalopathy; Hypoxic Ischemic Encephalopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Hypothermia

If randomized to hypothermia, plastic bags filled with ice wrapped in a washcloth were applied to the head and body for approximately 2 hours, then the infant was placed on an adult-size, water-circulating, cooling blanket (Cincinnati Sub-Zero Blanketrol II®, Cincinnati, OH), servo-controlled to rectal temperature to 33 ± 0.5 °C for 48 hours at the participating tertiary care center. Rewarming by 0.5°C per hour was begun after 48 hours of hypothermia.

Group Type: EXPERIMENTAL

hypothermia

Intervention Type: OTHER

Systemic hypothermia by Cincinnati Sub-Zero Blanketrol II®, servo-controlled to 33.0 degrees C rectal temperature, started within 6hours of hypoxic ischemic birth, and continued for 48hours

Normothermia

If randomized to normothermia, rectal temperatures were maintained at 37 ± 0.5 °C per standard neonatal intensive care unit practice, using adult-size, water-circulating, cooling blanket (Cincinnati Sub-Zero Blanketrol II®, Cincinnati, OH), servo-controlled to rectal temperature of 37 ± 0.5 if baby was febrile.

Group Type: PLACEBO_COMPARATOR

normothermia

Intervention Type: OTHER

Rectal temperatures in neonates receiving normothermia were maintained at 37.0+or -0.5 degrees C, using overhead warmer or Cincinnati Sub-Zero Blanketrol II®, servo-controlled to rectal temperature of 37.0 degrees C.

Interventions

hypothermia

Systemic hypothermia by Cincinnati Sub-Zero Blanketrol II®, servo-controlled to 33.0 degrees C rectal temperature, started within 6hours of hypoxic ischemic birth, and continued for 48hours

Intervention Type: OTHER

normothermia

Rectal temperatures in neonates receiving normothermia were maintained at 37.0+or -0.5 degrees C, using overhead warmer or Cincinnati Sub-Zero Blanketrol II®, servo-controlled to rectal temperature of 37.0 degrees C.

Intervention Type: OTHER

Other Intervention Names

whole body cooling

Eligibility Criteria

Inclusion Criteria

One clinical indication of hypoxic-ischemic injury

• cord gas pH ≤ 7.0 or base deficit ≥13,
• initial infant gas pH < 7.1,
• Apgar score ≤5 at 10 minutes,
• continued resuscitation after 5 min,
• fetal bradycardia with heart rate < 80 beats per minute lasting ≥15 min,
• postnatal event O2 sat <70% or arterial O2<35 for 20 min with ischemia

And two neurologic findings of neonatal encephalopathy, abnormalities of:

• tone,
• reflexes,
• state of consciousness,
• seizures,
• posturing,
• autonomic dysfunction

Exclusion Criteria

• Maternal chorioamnionitis,
• sepsis at birth,
• birth weight or head circumference <10%,
• presumed chromosomal abnormality

• Minimum Eligible Age: 35 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Dorothea D. Jenkins

Associate Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dorothea D Jenkins, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

References

Eicher DJ, Wagner CL, Katikaneni LP, Hulsey TC, Bass WT, Kaufman DA, Horgan MJ, Languani S, Bhatia JJ, Givelichian LM, Sankaran K, Yager JY. Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol. 2005 Jan;32(1):11-7. doi: 10.1016/j.pediatrneurol.2004.06.014.

Reference Type: RESULT

PMID: 15607598 (View on PubMed)

Eicher DJ, Wagner CL, Katikaneni LP, Hulsey TC, Bass WT, Kaufman DA, Horgan MJ, Languani S, Bhatia JJ, Givelichian LM, Sankaran K, Yager JY. Moderate hypothermia in neonatal encephalopathy: safety outcomes. Pediatr Neurol. 2005 Jan;32(1):18-24. doi: 10.1016/j.pediatrneurol.2004.06.015.

Reference Type: RESULT

PMID: 15607599 (View on PubMed)

Jenkins DD, Lee T, Chiuzan C, Perkel JK, Rollins LG, Wagner CL, Katikaneni LP, Bass WT, Kaufman DA, Horgan MJ, Laungani S, Givelichian LM, Sankaran K, Yager JY, Martin R. Altered circulating leukocytes and their chemokines in a clinical trial of therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy*. Pediatr Crit Care Med. 2013 Oct;14(8):786-95. doi: 10.1097/PCC.0b013e3182975cc9.

Reference Type: RESULT

PMID: 23897243 (View on PubMed)

Jenkins DD, Rollins LG, Perkel JK, Wagner CL, Katikaneni LP, Bass WT, Kaufman DA, Horgan MJ, Languani S, Givelichian L, Sankaran K, Yager JY, Martin RH. Serum cytokines in a clinical trial of hypothermia for neonatal hypoxic-ischemic encephalopathy. J Cereb Blood Flow Metab. 2012 Oct;32(10):1888-96. doi: 10.1038/jcbfm.2012.83. Epub 2012 Jul 18.

Reference Type: RESULT

PMID: 22805873 (View on PubMed)

Other Identifiers

R01NS038062

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NS38062

Identifier Type: -

Identifier Source: org_study_id