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| Name | Class |
|---|---|
| University of California, San Francisco | OTHER |
| Children's National Research Institute | OTHER |
| Children's Hospital Los Angeles | OTHER |
| St. Louis University |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Normothermia | Procedure | Usual care for first 72 hours for neonates with mild encephalopathy maintaining core temperature (36.5°C ± 1 C). |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 22-26 months of age. |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events SAE | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Infant neurological integrity as measured with HNNE | 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. |
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):
An acute perinatal event is defined by at least one of the following:
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:
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Term infants ≥ 36 weeks' gestation with evidence of both perinatal event fetal acidosis and encephalopathy on exam.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Lina Chalak, MD | Contact | 214-648-3903 | lina.chalak@utsouthwestern.edu | |
| Pollieanna Sepulveda, MSN, RN | Contact | 214-648-3698 | pollieanna.sepulveda@utsouthwestern.edu |
| Name | Affiliation | Role |
|---|---|---|
| Lina Chalak, MD | University of Texas Southwestern Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Texas Southwestern Medical Center | Recruiting | Dallas | Texas | 75208 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29095433 | Background | 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. | |
| 30250303 |
| Label | URL |
|---|---|
| Study website page for participants. | View source |
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| ID | Term |
|---|---|
| D020925 | Hypoxia-Ischemia, Brain |
| D002545 | Brain Ischemia |
| D002534 | Hypoxia, Brain |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| OTHER |
| Stanford University | OTHER |
| University of Utah | OTHER |
| University of Pittsburgh Medical Center | OTHER |
| Children's Hospital Medical Center, Cincinnati | OTHER |
| University College Cork | OTHER |
| The Children's Hospital of San Antonio | OTHER |
| Harvard University | OTHER |
| Washington University School of Medicine | OTHER |
| Sharp HealthCare | OTHER |
| The Cleveland Clinic | OTHER |
| University of Florida Health | OTHER |
| Emory University | OTHER |
| Nationwide Children's Hospital | OTHER |
| Children's Hospital of Orange County | OTHER |
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| 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. |
|
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 | 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 | 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 |
| Discharge |
| Infant neurological integrity as measured with HINE | 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 | 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 |
| Behavioral tendency CBCL | 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 | 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. |
| IFS-R | Impact on Family Scale - Revised | 9-12 months |
| IBQ-R | Infant Behavior Questionnaire Revised (very short) | 9-12months |
| 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. |
| 31301853 | Background | 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. |
| 30733613 | Background | 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. |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000860 | Hypoxia |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |