Project Details

Erythropoietin Monotherapy for Neonatal Encephalopathy in Low and Middle-income Countries (EMBRACE Trial)

Sudhin Thayyil, MD, DCH, FRCPCH, PhD

Summary

BACKGROUND: Approximately one million babies die every year, and many more sustain life-long disabilities from neonatal encephalopathy in low-and middle-income countries (LMICs). Unlike in high-income countries, cooling therapy is not effective in LMICs and may cause more harm. GAP: Erythropoietin is neuroprotective in preclinical models when used without hypothermia. A recent meta-analysis of Erythropoietin monotherapy (i.e. without hypothermia) in babies with neonatal encephalopathy including a total of 348 babies reported a reduction (Risk Ratio 0.62 (95% CI 0.40 to 0.98) in death or disability at 18 months. Hence as definitive trial of Erythropoietin is now warranted. HYPOTHESIS: Erythropoietin monotherapy will reduce the death or disability at 18-22 months after moderate or severe neonatal encephalopathy in term babies in LMICs. Method: Multi-country double-blind randomised controlled trial recruiting 504 full term babies from tertiary neonatal intensive care units in India, Sri Lanka and Bangladesh. Babies with moderate or severe encephalopathy on a structured neurological examination performed between 1 and 6 hours of birth will be randomly allocated to 500 U/kg of subcutaneous Erythropoietin (first dose will be given within 6 hours of birth) or placebo until day 9. Magnetic resonance imaging and spectroscopy will be performed at 2 week and neurodevelopmental outcomes will be assessed at 18 months using Bayley scales of infant and toddler development (Version IV). IMPACT: Erythropoietin is widely available in LMIC and is inexpensive. If Erythropoietin improves outcomes after neonatal encephalopathy, it can be readily used in LMIC as a clinical treatment leading to a substantial reduction in death or disability.