Background Preterm infants suffering from intraventricular haemorrhage (IVH) are at increased risk for neurodevelopmental impairment. Observational data suggest that recombinant human erythropoietin (EPO) aimed at preventing anaemia also improves long-term cognitive outcome in infants with IVH (Neubauer AP et al ., Annals Neurology, 2010). The recently completed first early high-dose EPO trial in very preterm infants did not raise any significant safety concerns (Fauchère J-C. et al ., ESPR Annual Meeting, 2012). Hypothesis: High-dose EPO improves long-term neurodevelopmental outcome in preterm infants with IVH.
Methods Design: Double blind, 1:1 randomised clinical study in 11 perinatal centres (Germany and Switzerland). Patients: 120 very preterm (gestational age <32 weeks) and/or very low birth weight (<1500 g) infants with IVH (>I°) diagnosed by cranial ultrasound during the first 4 days of life. Intervention: 5 intravenous applications of EPO (2000 U/kg) or placebo spread over 3 weeks. Primary objective: Neurodevelopmental outcome at 5 years of age (Kaufmann-ABC or Son-R). Secondary objectives: (1) safety; (2) MRI at term equivalent age to quantitatively analyse brain injury and growth; (3) psychomotor development at 2 years of age (BSID-III). Recruitment: March 2014 to February 2016.
Results and conclusions Given the fact that long-term neurodevelopmental outcome cannot be reliably assessed until preschool age, the primary outcome of this study providing evidence as to whether high-dose EPO improves restitution of brain damage in preterm infants will not be reported before 2021. However, MRI data can be reported much earlier. (Funded by the Swiss National Science Foundation; Clinical Trials Registry: NCT02076373).