Cool Prime Comparative Effectiveness Study for Mild HIE

NCT ID: NCT04621279

Last Updated: 2025-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

460 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-07-19

Study Completion Date

2029-01-01

Brief Summary

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To determine effectiveness of therapy to improve neurodevelopmental outcomes in infants with mild HIE. To determine the adverse effects of Therapeutic Hypothermia (TH) in mild HIE on the neonate and his/her family. Determine heterogeneity of the treatment effect across key subgroups obtained in the first 6 hours after birth prior to the decision to initiate therapy.

Detailed Description

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This study leverages practice variation within and across 15 participating sites to compare the effectiveness of TH versus normothermia for mild HIE on neurodevelopmental outcomes at 2 years of age.After standardizing all aspects of clinical care for mild HIE (except for TH vs. normothermia)we will enroll 460 infants with mild HIE into the longitudinal, observational comparative effectiveness study.The central aim of the comparative longitudinal cohort of mild HIE is (1) to compare the effectiveness of hypothermia to normothermia on neurodevelopmental outcomes at 2 years, (2) determine the adverse effects of TH on the infant and his/her family; and (3) determine the heterogeneity of treatment effects (moderating effect) across mild HIE subgroups as determined by physiological biomarkers obtained during the 6 hours window to initiate hypothermia. The decision to apply TH or normothermia will be entirely determined by practice parameters at each site.

Conditions

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Mild Hypoxic Ischemic Encephalopathy of Newborn

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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Mild HIE

Mild HIE identified in the first 6 hours of life according to the published PRIME study definition: newborn with evidence of encephalopathy (using the validated Sarnat Exam) NOT meeting prior cooling trials criteria.

Normothermia

Intervention Type PROCEDURE

Usual care for first 72 hours for neonates with mild encephalopathy maintaining core temperature (36.5°C ± 1 C).

Whole body therapeutic hypothermia

Intervention Type PROCEDURE

Whole-body therapeutic hypothermia (33.5°C ± 0.5°C) for 72 hours began by 6 hours of age for neonates with mild encephalopathy per site standard of care practice.

Interventions

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Normothermia

Usual care for first 72 hours for neonates with mild encephalopathy maintaining core temperature (36.5°C ± 1 C).

Intervention Type PROCEDURE

Whole body therapeutic hypothermia

Whole-body therapeutic hypothermia (33.5°C ± 0.5°C) for 72 hours began by 6 hours of age for neonates with mild encephalopathy per site standard of care practice.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Neonates born at ≥ 36 0/7 weeks
2. Mild Encephalopathy on neonatal neurologic exam within 6 hours after birth: defined as presence of at least 2 signs of mild, moderate, or severe encephalopathy with no more than 2 signs in the moderate or severe category.
3. Perinatal Acidosis based on at least one of the following (A or B):

1. pH ≤ 7.00 in any cord or first infant gas (arterial, venous, or capillary) within ≤ 60 min OR base deficit ≥ 16 in any cord or first infant gas (arterial, venous or capillary) within ≤ 60 min
2. If pH is between 7.01 and 7.15, OR base deficit is between 10 and 15.9 mmol/liter, OR blood gas is not available, an acute perinatal event is an additional criteria required (see below definition)

An acute perinatal event is defined by at least one of the following:

1. Apgar score at 10 min ≤ 5
2. Continued need for resuscitation at 10 min (chest compressions, bag mask ventilation, or positive pressure ventilation)
3. Uterine rupture, placental abruption, cord accident (prolapse, rupture, knot or tight nuchal cord)
4. maternal trauma, maternal hemorrhage, or cardiorespiratory arrest
5. fetal exsanguination from either vasa previa or feto-maternal hemorrhage, shoulder dystocia
6. Any evidence suggestive of acute perinatal event.

Infants are still eligible for enrollment in the COOLPRIME study if the cord or infant's first blood gas (arterial, venous, or capillary) is obtained \>60 minutes of life.

Exclusion Criteria

1. Gestational age at birth \< 36 0/7 weeks
2. Birth weight \< 1800gm
3. Head circumference \<30cm
4. Congenital or chromosomal anomaly associated with abnormal neurodevelopment or death
5. Moderate or Severe HIE of 3 or more moderate or severe abnormalities on COOLPRIME Sarnat exam within 6 hours of life
6. Any seizures within first six hours of life
7. Redirection of care is being considered
Minimum Eligible Age

36 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of California, San Francisco

OTHER

Sponsor Role collaborator

Children's National Research Institute

OTHER

Sponsor Role collaborator

Children's Hospital Los Angeles

OTHER

Sponsor Role collaborator

St. Louis University

OTHER

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role collaborator

University of Pittsburgh Medical Center

OTHER

Sponsor Role collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role collaborator

University College Cork

OTHER

Sponsor Role collaborator

The Children's Hospital of San Antonio

OTHER

Sponsor Role collaborator

Harvard University

OTHER

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role collaborator

Sharp HealthCare

OTHER

Sponsor Role collaborator

The Cleveland Clinic

OTHER

Sponsor Role collaborator

University of Florida Health

OTHER

Sponsor Role collaborator

Emory University

OTHER

Sponsor Role collaborator

Nationwide Children's Hospital

OTHER

Sponsor Role collaborator

Children's Hospital of Orange County

OTHER

Sponsor Role collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Lina Chalak

PROFESSOR

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lina Chalak, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center

Locations

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University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Lina Chalak, MD

Role: CONTACT

214-648-3903

Pollieanna Sepulveda, MSN, RN

Role: CONTACT

214-648-3698

Facility Contacts

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Pollieanna M Sepulveda

Role: primary

2146483698

References

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Prempunpong C, Chalak LF, Garfinkle J, Shah B, Kalra V, Rollins N, Boyle R, Nguyen KA, Mir I, Pappas A, Montaldo P, Thayyil S, Sanchez PJ, Shankaran S, Laptook AR, Sant'Anna G. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol. 2018 Jan;38(1):80-85. doi: 10.1038/jp.2017.164. Epub 2017 Nov 2.

Reference Type BACKGROUND
PMID: 29095433 (View on PubMed)

Chalak LF, Nguyen KA, Prempunpong C, Heyne R, Thayyil S, Shankaran S, Laptook AR, Rollins N, Pappas A, Koclas L, Shah B, Montaldo P, Techasaensiri B, Sanchez PJ, Sant'Anna G. Prospective research in infants with mild encephalopathy identified in the first six hours of life: neurodevelopmental outcomes at 18-22 months. Pediatr Res. 2018 Dec;84(6):861-868. doi: 10.1038/s41390-018-0174-x. Epub 2018 Sep 13.

Reference Type BACKGROUND
PMID: 30250303 (View on PubMed)

Chalak LF, Adams-Huet B, Sant'Anna G. A Total Sarnat Score in Mild Hypoxic-ischemic Encephalopathy Can Detect Infants at Higher Risk of Disability. J Pediatr. 2019 Nov;214:217-221.e1. doi: 10.1016/j.jpeds.2019.06.026. Epub 2019 Jul 10.

Reference Type BACKGROUND
PMID: 31301853 (View on PubMed)

El-Dib M, Inder TE, Chalak LF, Massaro AN, Thoresen M, Gunn AJ. Should therapeutic hypothermia be offered to babies with mild neonatal encephalopathy in the first 6 h after birth? Pediatr Res. 2019 Mar;85(4):442-448. doi: 10.1038/s41390-019-0291-1. Epub 2019 Jan 16.

Reference Type BACKGROUND
PMID: 30733613 (View on PubMed)

Related Links

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https://parents.coolprime.org/

Study website page for participants.

Other Identifiers

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STU-2022-0714

Identifier Type: -

Identifier Source: org_study_id

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