- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04621279
Cool Prime Comparative Effectiveness Study for Mild HIE (COOLPRIME)
December 5, 2023 updated by: Lina Chalak, University of Texas Southwestern Medical Center
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.
Study Overview
Status
Recruiting
Intervention / Treatment
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 Type
Observational
Enrollment (Estimated)
460
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Lina Chalak, MD
- Phone Number: 214-648-3903
- Email: lina.chalak@utsouthwestern.edu
Study Contact Backup
- Name: Pollieanna Sepulveda, MSN, RN
- Phone Number: 214-648-3698
- Email: pollieanna.sepulveda@utsouthwestern.edu
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Recruiting
- Emory University Hospital
-
Contact:
- Megan Moran
- Email: Mmegan.moran@emory.edu
-
-
Texas
-
Dallas, Texas, United States, 75208
- Recruiting
- University of Texas Southwestern Medical Center
-
Contact:
- Pollieanna M Sepulveda
- Phone Number: 214-648-3698
- Email: pollieanna.sepulveda@utsouthwestern.edu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
8 months and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Sampling Method
Non-Probability Sample
Study Population
Term infants ≥ 35 weeks' gestation with evidence of both perinatal event fetal acidosis and encephalopathy on exam.
Description
Inclusion Criteria:
Infants must meet all 3 inclusion criteria
- Neonates born at ≥ 35 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 < 35 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Other
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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.
|
Usual care for first 72 hours for neonates with mild encephalopathy maintaining core temperature (36.5°C ± 1 C).
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
22-26 months of age.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Discharge (approximately 7 days)
|
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".
|
3-4 months
|
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.
|
3-4 months
|
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.
|
3-4 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
22-26 months of age.
|
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.
|
22-26 months of age.
|
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.
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Discharge
|
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 - 4 months
|
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.
|
22-26 months
|
IFS-R
Time Frame: 9-12 months
|
Impact on Family Scale - Revised
|
9-12 months
|
IBQ-R
Time Frame: 9-12months
|
Infant Behavior Questionnaire Revised (very short)
|
9-12months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Lina Chalak, MD, University of Texas Southwestern Medical Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General 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.
- 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.
- 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. Erratum In: J Pediatr. 2020 Mar;218:e2.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 19, 2023
Primary Completion (Estimated)
October 1, 2027
Study Completion (Estimated)
January 1, 2029
Study Registration Dates
First Submitted
October 23, 2020
First Submitted That Met QC Criteria
November 2, 2020
First Posted (Actual)
November 9, 2020
Study Record Updates
Last Update Posted (Estimated)
December 13, 2023
Last Update Submitted That Met QC Criteria
December 5, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- STU-2022-0714
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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