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NCT Number: NCT04621279

Cool Prime Comparative Effectiveness Study for Mild HIE

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.

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Key information

Conditions

Mild Hypoxic Ischemic Encephalopathy of Newborn Brain Diseases Brain Ischemia Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Hypoxia Hypoxia, Brain Hypoxia-Ischemia, Brain Nervous System Diseases Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Respiratory Vascular Diseases

Age range

36 week and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Texas Southwestern Medical Center

Dallas, Texas, 75208, United States

Location status: Recruiting

Location contact

Pollieanna M Sepulveda

CONTACT

[email protected]

2146483698

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Infants must meet all 3 inclusion criteria

  • Neonates born at ≥ 36 0/7 weeks
  • 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.
  • Perinatal Acidosis based on at least one of the following (A or B):
  • 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
  • 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:

  • Apgar score at 10 min ≤ 5
  • Continued need for resuscitation at 10 min (chest compressions, bag mask ventilation, or positive pressure ventilation)
  • Uterine rupture, placental abruption, cord accident (prolapse, rupture, knot or tight nuchal cord)
  • maternal trauma, maternal hemorrhage, or cardiorespiratory arrest
  • fetal exsanguination from either vasa previa or feto-maternal hemorrhage, shoulder dystocia
  • 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

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

Treatment and study plan

Normothermia

Procedure

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

Whole body therapeutic hypothermia

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.

Primary outcomes

  1. Effectiveness of normothermia in infants as measured by Composite Bayley IV score

    Time frame: 22-26 months of age.

    Effectiveness of normothermia in infants is measured by Composite Bayley IV score scale, which is. an extensive formal developmental assessment tool for diagnosing developmental delays in early childhood. Possible scores range from 55- 120 where lower scores indicate worse outcome.

Secondary outcomes

  1. Adverse events SAE

    Time frame: Discharge (approximately 7 days)

    Safety will be measured by the presence or absence of a serious adverse event (SAE) at discharge.

  2. Parent-Infant stress and bonding as measured by MIBS

    Time frame: 3-4 months

    Parent-Infant stress and bonding is measured by Mother-to-infant bonding (MIBS) scale, which is a validated questionnaire with good psychometric properties that assesses the mother's feelings towards infant (bondedness) from birth to 4 months. Possible scores range from 0-3, where 0 indicates "not at all" and 3, "very much".

  3. Parent-Infant stress and bonding as measured by IBQR

    Time frame: 3-4 months

    Parent-Infant stress and bonding is measured by Infant Behavior Questionnaire-Revised (IBQR) which measures differences in reactivity and regulation, and the structure of infant temperament and its relation to parental family functioning. Item scores were summed according to IBQR scoring rules to create scores on the 14 scales, with higher scores indicating greater levels of that temperament dimension.

  4. Parent-Infant stress and bonding as measured by PSI

    Time frame: 3-4 months

    Parent-Infant stress and bonding is measured by Parenting Stress Index (PSI) which is an abbreviated version of the full-length test with 36 items in three domains (Parental Distress, Parent-Child Dysfunctional Interaction, and Difficult Child) that combine to form a Total Stress scale, which helps identify families that are most in need of support services. In general, items are scored using the following 5-point scale: 1) SA (Strongly Agree), 2) A (Agree), 3) NS (Not Sure), 4) D (Disagree), 5) SD (Strongly Disagree). Responses to both the overall stress score and the three subscales are summed to generate representative scores, resulting the total stress score, perceptions of child behavioral problems, parenting distress, and parent-child dysfunctional interactions.

Other outcomes

  1. Infant neurological integrity as measured with HNNE

    Time frame: Discharge

    Infant neurological integrity is measured with HNNE (Hammersmith Neonatal Neurological Exams), which is used to assess tone, spontaneous movements, reflexes, and visual and auditory attention allowing for a continuum of assessment from birth to 2 years. The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. The maximum global score is 78.

  2. Infant neurological integrity as measured with HINE

    Time frame: 3 - 4 months

    Infant neurological integrity is measured with HINE (Hammersmith Infant Neurological Exams), which is used to assess tone, spontaneous movements, reflexes, and visual and auditory attention allowing for a continuum of assessment from birth to 2 years. The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. The maximum global score is 78.

  3. Infant neurological integrity as measured with HINE

    Time frame: 22-26 months

    Infant neurological integrity is measured with HINE (Hammersmith Infant Neurological Exams), which is used to assess tone, spontaneous movements, reflexes, and visual and auditory attention allowing for a continuum of assessment from birth to 2 years. The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. The maximum global score is 78.

  4. Behavioral tendency CBCL

    Time frame: 22-26 months of age.

    The Child Behavior Checklist-parent report (CBCL) will provide a profile of behavior and social functioning validated in relation to age and gender.

  5. Composite PARCA-R

    Time frame: 22-26 months of age.

    The Parent Report of Children's Abilities-Revised (PARCA-R) is used against the Mental Development Index of the Bayley Scales.

  6. IFS-R

    Time frame: 9-12 months

    Impact on Family Scale - Revised

  7. IBQ-R

    Time frame: 9-12months

    Infant Behavior Questionnaire Revised (very short)

Study contacts

Contact information is provided by the study sponsor or research team.

Lina Chalak, MD

CONTACT

[email protected]

214-648-3903

Pollieanna Sepulveda, MSN, RN

CONTACT

[email protected]

214-648-3698

Sponsors and collaborators

Lead sponsor

University of Texas Southwestern Medical Center

Other

Collaborators

  • Children's Hospital Los Angeles
  • Children's Hospital Medical Center, Cincinnati
  • Children's Hospital of Orange County
  • Children's National Research Institute
  • Emory University
  • Harvard University
  • Nationwide Children's Hospital
  • Sharp HealthCare
  • St. Louis University
  • Stanford University
  • The Children's Hospital of San Antonio
  • The Cleveland Clinic
  • University College Cork
  • University of California, San Francisco
  • University of Florida Health
  • University of Pittsburgh Medical Center
  • University of Utah
  • Washington University School of Medicine

Registry information

Official study title

COOLPRIME: Comparative Effectiveness for Cooling Prospectively Infants With Mild Encephalopathy

Acronym: COOLPRIME

Important dates

Study start
2023
Primary completion
2026
Study completion
2029
First posted
Nov 9, 2020
Registry last updated
May 5, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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