Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Caffeine for Hypoxic-Ischemic Encephalopathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03913221
Recruitment Status : Recruiting
First Posted : April 12, 2019
Last Update Posted : August 12, 2020
Sponsor:
Collaborator:
Thrasher Research Fund
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
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)
Primary Purpose: Treatment
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 2021
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Caffeine

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 24 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented informed consent from parent or guardian
  • ≥ 36 weeks gestational age at birth
  • Receiving therapeutic hypothermia for a diagnosis of HIE
  • Intravenous (IV) access
  • Postnatal age < 24 hours

Exclusion Criteria:

  • Receiving > 1 anti-epileptic drug for seizures
  • Sustained (>4 hours) heart rate > 180 beats per minute
  • Known major congenital anomaly
  • Any condition which would make the participant, in the opinion of the investigator, unsuitable for the study
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Jennifer Talbert, MS, RN 984-974-7865 jlhamm@email.unc.edu

Locations
Layout table for location information
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    wesley.jackson@unc.edu   
Contact: Matthew M Laughon, MD, MPH    984-974-7851    matt_laughon@med.unc.edu   
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Thrasher Research Fund
Investigators
Layout table for investigator information
Principal Investigator: Wesley M Jackson, MD, MPH University of North Carolina, Chapel Hill
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications:

Layout table for additonal information
Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT03913221    
Other Study ID Numbers: 19-0348
First Posted: April 12, 2019    Key Record Dates
Last Update Posted: August 12, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Time Frame: Beginning 9 months and ending 36 months following article publication.
Access Criteria: 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.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Brain Diseases
Brain Ischemia
Hypoxia-Ischemia, Brain
Ischemia
Hypoxia
Pathologic Processes
Central Nervous System Diseases
Nervous System Diseases
Signs and Symptoms, Respiratory
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Hypoxia, Brain
Caffeine
Caffeine citrate
 Citric Acid
Sodium Citrate
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Central Nervous System Stimulants
Physiological Effects of Drugs
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents