Mild Hypoxic Ischemic Encephalopathy of NewbornCOOLPRIMENCT04621279
Cool Prime Comparative Effectiveness Study for Mild HIE
An observational study of Mild Hypoxic Ischemic Encephalopathy of Newborn, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 36 weeks and older
- Conditions the study is for
- Mild Hypoxic Ischemic Encephalopathy of Newborn
- What is being tested?
- Normothermia and Whole body therapeutic hypothermia
- Type of treatment
- Surgery or procedure
- How many people
- 460 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jul 2023to 1 Jan 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 36 weeks and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Term infants ≥ 36 weeks' gestation with evidence of both perinatal event fetal acidosis and encephalopathy on exam.
Who may be able to join
- 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)
Show all 14Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75208
Pollieanna M Sepulveda, 2146483698, pollieanna.sepulveda@utsouthwestern.edu
About this study
Official title: COOLPRIME: Comparative Effectiveness for Cooling Prospectively Infants With Mild Encephalopathy
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.
Read the detailed description
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.
- Being tested
- Normothermia, Whole body therapeutic hypothermia
- Keywords
- mild HIE (Hypoxic Ischemic Encephalopathy), neonatal encephalopathy, brain ischemia, brain hypoxia
- Medical subject headings
- Hypoxia-Ischemia, Brain, Brain Ischemia, Hypoxia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NormothermiaProcedure or surgery
Usual care for first 72 hours for neonates with mild encephalopathy maintaining core temperature (36.5°C ± 1 C).
Whole body therapeutic hypothermiaProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Normothermia; Procedure: Whole body therapeutic hypothermia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effectiveness of normothermia in infants as measured by Composite Bayley IV score
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.
Measured: 22-26 months of age.
Secondary outcomes (4)
Adverse events SAE
Safety will be measured by the presence or absence of a serious adverse event (SAE) at discharge.
Measured: Discharge (approximately 7 days)
Parent-Infant stress and bonding as measured by MIBS
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".
Measured: 3-4 months
Parent-Infant stress and bonding as measured by IBQR
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.
Measured: 3-4 months
Parent-Infant stress and bonding as measured by PSI
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.
Measured: 3-4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2020
- Study start19 Jul 2023
- Primary completion31 Oct 2026 (estimated)
- Study completion1 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Mild Hypoxic Ischemic Encephalopathy of NewbornStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 460 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, San Francisco, Children's National Research Institute, Children's Hospital Los Angeles, St. Louis University, Stanford University, University of Utah, University of Pittsburgh Medical Center, Children's Hospital Medical Center, Cincinnati, University College Cork, The Children's Hospital of San Antonio, Harvard University, Washington University School of Medicine, Sharp HealthCare, The Cleveland Clinic, University of Florida Health, Emory University, Nationwide Children's Hospital, Children's Hospital of Orange County, Parkland Health and Hospital System
- Responsible party
- Principal investigator, Lina Chalak, University of Texas Southwestern Medical Center
- Investigators
- Lina Chalak, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04621279
- Sponsor's protocol ID
- STU-2022-0714
- Acronym
- COOLPRIME
- Status last verified
- Sep 2026
- First submitted
- 23 Oct 2020
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 29095433Chalak 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.
PubMed 30250303Chalak 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.
PubMed 31301853El-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.
PubMed 30733613
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COOLPRIME: Comparative Effectiveness for Cooling Prospectively Infants With Mild Encephalopathy
- ClinicalTrials.gov ID
- NCT04621279
- Acronym / sponsor ID
- COOLPRIME / STU-2022-0714
- Keywords
- mild HIE (Hypoxic Ischemic Encephalopathy), neonatal encephalopathy, brain ischemia, brain hypoxia
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 460 participants (estimated)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- University of California, San Francisco, Children's National Research Institute, Children's Hospital Los Angeles, St. Louis University, Stanford University, University of Utah, University of Pittsburgh Medical Center, Children's Hospital Medical Center, Cincinnati, University College Cork, The Children's Hospital of San Antonio, Harvard University, Washington University School of Medicine, Sharp HealthCare, The Cleveland Clinic, University of Florida Health, Emory University, Nationwide Children's Hospital, Children's Hospital of Orange County, Parkland Health and Hospital System
- Study start
- 19 Jul 2023 (actual)
- Primary completion
- 31 Oct 2026 (estimated)
- Study completion
- 1 Jan 2029 (estimated)
- First posted
- 9 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mild HIE | – | Procedure: Normothermia, Procedure: Whole body therapeutic hypothermiaMild 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. |
Who may qualify
- Ages
- 36 weeks and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Term infants ≥ 36 weeks' gestation with evidence of both perinatal event fetal acidosis and encephalopathy on exam.
Key inclusion criteria (14 listed)
- 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):
- Apgar score at 10 min ≤ 5
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NormothermiaUsual care for first 72 hours for neonates with mild encephalopathy maintaining core temperature (36.5°C ± 1 C). | Procedure or surgery | Mild HIE |
| Whole body therapeutic hypothermiaWhole-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. | Procedure or surgery | Mild HIE |
Primary outcome
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.
4 secondary outcomes
Adverse events SAE
Time frame: Discharge (approximately 7 days)
Parent-Infant stress and bonding as measured by MIBS
Time frame: 3-4 months
Parent-Infant stress and bonding as measured by IBQR
Time frame: 3-4 months
Parent-Infant stress and bonding as measured by PSI
Time frame: 3-4 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- Background: PubMed 29095433Prempunpong 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.
- Background: PubMed 30250303Chalak 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.
- Background: PubMed 31301853Chalak 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.
- Background: PubMed 30733613El-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.
- Study website page for participants.Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lina Chalak, MD principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mild Hypoxic Ischemic Encephalopathy of Newborn, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lina Chalak, MD (214-648-3903, lina.chalak@utsouthwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effectiveness of normothermia in infants as measured by Composite Bayley IV score (time frame: 22-26 months of age.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04621279, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.