Brain Injury, Erythropoietin, Infant, Premature, Intraventricular Hemorrhage, Neurodevelopmental Outcomes, Periventricular Leukomalacia, Randomized Clinical Trial
Conditions
Keywords
Extreme Prematurity, Erythropoietin, Perinatal Brain Injury, Intraventricular Hemorrhage, Periventricular Leukomalacia, Neurodevelopmental Outcomes, Randomized Clinical Trial
Brief summary
The highest risk for perinatal brain injury occurs among extremely premature infants who weigh less than 1250 grams at birth. Such perinatal brain injury is currently irreversible, associated with neurodevelopmental disability, and without adequate treatment modalities. Research in recent years suggest in both animal and human studies that erythropoietin (Epo) may have significant neuroprotective effects. Given the historical safe medical profile of Epo when used for anemia of prematurity but the likely need for a greater dosage regimen for activation of neuroprotective pathways against neonatal brain injury, we therefore propose this phase II study of high-dose Epo in very low birth weight infants for the prevention and/or attenuation of prematurity-related cerebral hemorrhagic-ischemic injury.
Detailed description
Eligible extremely premature infants will be enrolled in this double-blind, placebo-controlled randomized trial from the neonatal intensive care unit at Morristown Memorial Hospital (Morristown, New Jersey). Subjects will be enrolled within the first 24 hours of life and randomly assigned to receive Epo or saline vehicle placebo. Standard NICU care will be provided to all subjects. Serial exams, CBC-d, reticulocyte counts, serum Epo levels, serial HUS, and head MRI will be collected at established time points during the study period. At 18 to 22 months corrected age, subjects will undergo a neurodevelopmental evaluation assessing for cerebral palsy, Bayley Scores of Infant Development-II (BSID-II) Mental Development Index (MDI), BSID-II Psychomotor Development Index (PDI), bilateral hearing aid use, and visual impairment.
Interventions
DRUGErythropoietin
5 of first 10 subjects (Group 1): 400 units/kg/dose once daily for 7 days 5 of next 10 subjects (Group 2): 800 units/kg/dose once daily for 7 days 20 of next 30 subjects (Group 3): 1000 units/kg/dose once daily for 7 days administered i.v. over 1 hour. The volume of the study drug will be 1 mL in a 1 mL Tuberculin syringe to be administered over 1 hour.
DRUGSaline placebo
Saline vehicle at a volume of 1 mL given over 1 hour intravenously once a day for the first seven days of life.
Sponsors
Atlantic Health System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Hours
Healthy volunteers
Yes
Inclusion criteria
* 500 to 1250 grams at birth * Less than 32 weeks gestation at birth * Less than 24 hours of life at time of enrollment
Exclusion criteria
* Congenital anomalies (chromosomal, CNS, cardiac, GI, pulmonary) * Seizures within first 24 hours of life * Severe neutropenia (ANC \< 500 cells/microL) within first 24 hours of life * Polycythemia (Hct \> 65%) within first 24 hours of life * Thrombocytopenia (platelets \< 50K cells/microL) within first 24 hours of life * Hypertension (SBP \> 100mmHg) without vasopressor support within first 24 hours of life
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Neurodevelopmental evaluations at 18 to 22 months corrected age (cerebral palsy, Bayley Scores of Infant Development Mental Development Index (MDI), Psychomotor Development Index (PDI), bilateral hearing aid use, and visual impairment) | 18-22 months corrected age |
Secondary
| Measure | Time frame |
|---|---|
| Severe intraventricular hemorrhage | First ten days of life |
| Polycythemia, neutropenia, thrombocytopenia, hypertension, sepsis, hemorrhage, seizure | NICU hospitalization |
Countries
United States
Outcome results
None listed