Kim Annink

177 ALBINO trial: study protocol Secondly, safety of early postnatal intravenous allopurinol will be evaluated, as well as the pharmacokinetic profile of intravenous allopurinol and the short-term effect of early allopurinol on brain injury assessed by magnetic resonance imaging (MRI) of the brain, cerebral ultrasound, heart function assessed by echocardiography, electro-encephalography (EEG), and biochemical biomarkers. Trial design The ALBINO trial is a European double-blinded randomized placebo-controlled parallel group multicenter trial for superiority of allopurinol versus placebo (mannitol) in addition to therapeutic hypothermia where indicated (Phase III). More than 60 hospitals in 10 countries will participate in this study, and ALBINO may expand to additional sites in further countries, after appropriate approvals have been obtained from ethics committees and authorities. Population Term and near-term infants (≥36 weeks) with severe perinatal asphyxia and potentially evolving encephalopathy can be included in the ALBINO trial. Inclusion criteria Infants must meet at least one of the following five criteria of severe perinatal asphyxia: 1) umbilical or postnatal blood gas within 30 min after birth with a pH <7.0 or 2) with a base deficit ≥16 mmol/l; 3) need for ongoing cardiac massage at/beyond 5 minutes postnatally; 4) need for adrenalin administration during resuscitation and/or 5) Apgar score ≤5 at 10 minutes after birth. Further, the infant must meet two out of the following four criteria for potentially evolving encephalopathy to participate in the study: 1) altered state of consciousness (reduced or absent response to stimulation or hyperexcitability); 2) severe muscular hypotonia or hypertonia; 3) absent or insufficient spontaneous respiration (i.e. gasping only) with need for respiratory support at 10 minutes postnatally and/or 4) abnormal primitive reflexes (absent suck/gag/ corneal/Moro reflex) or abnormal movements (i.e. potential clinical correlates of seizure activity). Exclusion criteria Infants will be excluded if the gestational age is below 36 weeks, birth weight is below 2500 gram, in the presence of severe congenital malformations or syndromes 8