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| ID | Type | Description | Link |
|---|---|---|---|
| 1K23HD111623-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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This is a phase Ib, open-label, dose-validating and safety study of caffeine in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia.
In a previous phase I trial (NCT03913221), the investigators characterized the pharmacokinetics (PK) of caffeine in the setting of HIE and therapeutic hypothermia using a population PK model. This is an open-label study of caffeine citrate in neonates with HIE to validate the population PK model and determine optimal dosing for HIE.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lower loading dose (20 mg/kg) | Active Comparator | Within 24 hours after delivery, participants will receive a loading dose of 20 mg/kg caffeine citrate IV. |
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| Higher loading dose (30 mg/kg) | Active Comparator | Within 24 hours after delivery, participants will receive a loading dose of 30 mg/kg caffeine citrate IV. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Caffeine citrate 20 mg/kg | Drug | Following loading dose of 20 mg/kg of caffeine citrate IV, participants will receive 2 daily doses of 10 mg/kg caffeine citrate IV. |
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| Measure | Description | Time Frame |
|---|---|---|
| Apparent Caffeine Clearance | Clearance is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Caffeine concentrations will be used to calculate population estimates of caffeine clearance, with inter-individual variabilty and residual variabilty . | 7 samples will be collected after the first dose of study drug and up to 72 hours after final dose of study drug |
| Volume of Distribution of Caffeine | Caffeine concentrations will be used to calculate population estimates of volume of distribution with inter-individual variability and residual variability. | 7 samples will be collected after the first dose of study drug and up to 72 hours after final dose of study drug |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Pre-Specified Adverse Events | Safety will be determined by the number of participants with the following: seizures requiring > 1 anti-epileptic drug, necrotizing enterocolitis defined as Bell Stage II or higher, hypoglycemia defined as point-of-care blood glucose < 30 mg/dL, and hyperglycemia defined as point-of-care blood glucose >200 mg/dL. | From the first dose of caffeine to 7 days following the final dose. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wesley M Jackson, MD, MPH | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of North Carolina at Chapel Hill Newborn Critical Care Center | Chapel Hill | North Carolina | 27599 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26387012 | Background | Shankaran S, McDonald SA, Laptook AR, Hintz SR, Barnes PD, Das A, Pappas A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal Magnetic Resonance Imaging Pattern of Brain Injury as a Biomarker of Childhood Outcomes following a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy. J Pediatr. 2015 Nov;167(5):987-93.e3. doi: 10.1016/j.jpeds.2015.08.013. Epub 2015 Sep 16. | |
| 26169430 |
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Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
Beginning 9 months and ending 36 months following article publication.
Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Sep 10, 2024 | Jun 16, 2026 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D020925 | Hypoxia-Ischemia, Brain |
| ID | Term |
|---|---|
| D002545 | Brain Ischemia |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C026189 | caffeine citrate |
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The first cohort of 8 infants will receive a lower loading dose of caffeine. Following a safety review, an additional 8 infants will receive a higher loading dose.
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| Caffeine citrate 30 mg/kg | Drug | Following loading dose of 30 mg/kg of caffeine citrate IV, participants will receive 2 daily doses of 10 mg/kg caffeine citrate IV. |
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| Number of Participants with Abnormal MRI Brain Finding Score | Preliminary effectiveness assessed using the NICHD Neonatal Research Network MRI scoring system that categorizes severity of brain injury in the Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy. Abnormal MRI is defined as any score >0.
| During initial hospitalization, typically 3-5 postnatal days |
| Number of Participants with Death or Neurodevelopmental Impairment | Preliminary effectiveness assessed based on death or neurodevelopmental impairment defined as: diagnosis of cerebral palsy, hearing impairment requiring hearing aids, blindness, or cognitive, language, or motor score < 85 on the Bayley Scales of Infant and Toddler Development- Fourth Edition. | 18-24 months of age |
| Novant Health New Hanover Regional Medical Center |
| Wilmington |
| North Carolina |
| 28401 |
| United States |
| Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, Kent AL. Neonatal Acute Kidney Injury. Pediatrics. 2015 Aug;136(2):e463-73. doi: 10.1542/peds.2014-3819. Epub 2015 Jul 13. |
| 37587184 | Background | Jackson W, Gonzalez D, Greenberg RG, Lee YZ, Laughon MM. A phase I trial of caffeine to evaluate safety in infants with hypoxic-ischemic encephalopathy. J Perinatol. 2024 Apr;44(4):508-512. doi: 10.1038/s41372-023-01752-y. Epub 2023 Aug 16. |
| D009422 | Nervous System Diseases |
| D002534 | Hypoxia, Brain |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000860 | Hypoxia |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |