Caffeine for Hypoxic-Ischemic Encephalopathy
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|ClinicalTrials.gov Identifier: NCT03913221|
Recruitment Status : Recruiting
First Posted : April 12, 2019
Last Update Posted : July 19, 2019
Hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia is common and often fatal. Therapeutic hypothermia reduces mortality and morbidity in infants with HIE. Even with the widespread use of therapeutic hypothermia, ~60% of infants with HIE die or have neurodevelopmental impairment. As a result, there is an urgent, unmet public health need to develop adjuvant therapies to improve survival and neurodevelopmental outcomes in this population.
Caffeine may offer neuroprotection for infants with HIE by blocking adenosine receptors in the brain and reducing neuronal cell death. In animal models of HIE, caffeine reduces white matter brain injury. Drugs in the same class as caffeine (i.e., methylxanthines) have been shown to be protective against acute kidney injury in the setting of HIE. However, their safety and efficacy have not been studied in the setting of therapeutic hypothermia and their effect on neurological outcomes is not known. Since these drugs reduce injury to the kidney in infants with HIE, they may also reduce injury to the brain.
This phase I study will evaluate the pharmacokinetics, safety, and preliminary effectiveness of caffeine as an adjuvant therapy to improve neurodevelopmental outcomes in infants with HIE.
|Condition or disease||Intervention/treatment||Phase|
|Hypoxic-Ischemic Encephalopathy||Drug: Caffeine Citrate 5 mg/kg Drug: Caffeine Citrate 10 mg/kg||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||The first cohort of 9 infants will receive a lower maintenance dose of caffeine. Following a safety review, an additional 9 infants will receive a higher maintenance dose.|
|Masking:||None (Open Label)|
|Official Title:||Pharmacokinetics and Safety of Caffeine in Neonates With Hypoxic-Ischemic Encephalopathy|
|Actual Study Start Date :||July 12, 2019|
|Estimated Primary Completion Date :||August 2020|
|Estimated Study Completion Date :||June 2021|
Active Comparator: Low Dose Caffeine (5 mg/kg)
Within 24 hours of delivery, participants will receive low dose administration of Caffeine citrate.
Drug: Caffeine Citrate 5 mg/kg
Loading dose of caffeine 20 mg/kg IV followed by two daily doses of 5 mg/kg IV.
Other Name: Cafcit
Active Comparator: High Dose Caffeine (10 mg/kg)
Within 24 hours of delivery, participants will receive high dose administration of Caffeine citrate.
Drug: Caffeine Citrate 10 mg/kg
Loading dose of caffeine 20 mg/kg IV followed by two daily doses of 10 mg/kg IV.
Other Name: Cafcit
- Area Under Plasma Concentration-time at Time t (AUC0-t) for Caffeine [ Time Frame: 7 samples will be collected with the following optimal sampling windows: 0-15 minutes, 30-60 minutes, 1-3 hours, 3-6 hours, 6-12 hours, 12-18 hours, 15 minutes prior to next dose. ]AUC0-t defines area under the plasma concentration-time curve (AUC) from administration to the last quantifiable concentration at time t.
- Incidence of seizures and necrotizing enterocolitis, which are potential complications of caffeine exposure [ Time Frame: From the first dose of caffeine to 7 days following the final dose. ]Incidence of seizure activity requiring >1 anti-epileptic medication. Necrotizing enterocolitis defined as Bell Stage II or III.
- Number of participants with abnormal MRI brain findings based on NICHD Neonatal Research Network score [ Time Frame: During initial hospitalization, approximately 7-14 postnatal days ]
The NICHD Neonatal Research Network developed and validated an MRI scoring system that categorizes severity of brain injury in the Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy.
- Score 0: Normal T2 MRI
- Score 1A: Minimal cerebral lesions only with involvement of basal ganglia, thalamus
- Score 1B: Extensive cerebral lesions
- Score 2A: Basal ganglia thalamic, anterior or posterior limb of internal capsule, or watershed infarction
- Score 2B: 2A with cerebral lesions
- Score 3: Hemispheric devastation
- Number of participants with a Bayley Scales of Infant Development (BSID-III) cognitive, language, or motor composite score < 85 [ Time Frame: 18-24 months of age ]The BSID--III is a series of measurements to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers and consists of a series of developmental play tasks. The composite scores are scaled to a metric with a range of 40 to 160, a mean of 100, and a standard deviation of 15. Therefore, children with a composite score < 85 are 1 standard deviation below the mean in that area.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03913221
|Contact: Jennifer Talbert, MS, RNfirstname.lastname@example.org|
|United States, North Carolina|
|The University of North Carolina at Chapel Hill Newborn Critical Care Center||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Wesley M Jackson, MD, MPH 984-215-3449 email@example.com|
|Contact: Matthew M Laughon, MD, MPH 984-974-7851 firstname.lastname@example.org|
|Principal Investigator:||Wesley M Jackson, MD, MPH||University of North Carolina, Chapel Hill|