Apply to trial NCT05617833

Safety of Erythropoietin and Melatonin for Very Preterm Infants With Intraventricular Hemorrhage

Very preterm infants are prone to numerous medical complications with lifelong impact. Amongst the most serious neurologically are white matter injury (WMI), intraventricular hemorrhage (IVH) and the subsequent progression to posthemorrhagic hydrocephalus (PHH). Currently, the only treatment for PHH is surgery, most commonly with shunts that are prone to malfunction across the lifespan. Preclinical data show that melatonin (MLT) and erythropoietin (EPO), when administered in a sustained dosing regimen, may promote neuro-repair, including the progression from early postnatal IVH to subsequent PHH. The investigators will perform a Phase I, single institution, randomized, double-blind trial for very preterm infants with IVH and WMI to define a safe combination dose of MLT and EPO. A maximum of 60 very preterm neonates with IVH and/or moderate to severe WMI will be enrolled, treated through 33w6/7d, and followed to 37w6/7d. Neonates will be randomized 3:1 between MLT+EPO and placebo, with all receiving standard of care. The primary endpoint is a composite serious adverse event (SAE)/dose limiting toxicity (DLT). The investigators hypothesize that the MLT+EPO SAE/DLT rate will not be higher than the placebo rate. Secondary outcomes will be rate of co-morbidities of preterm birth. Exploratory data, collected to guide design of future clinical trials for efficacy, will include serial neuro-imaging metrics acquired from clinical images, serial neonatal neurodevelopmental examinations, serum and urine MLT and EPO levels, liquid and gut microbiome biomarkers. Successful implementation of this initial safety trial will provide essential data to guide the next stage of clinical trials to test if sustained MLT+EPO treatment can reduce neurological deficits, including the need for surgical intervention and the lifelong burden of shunted hydrocephalus.