Introduction: Neonatal brain damage due to hypoxic-ischemic event is a major burden in the western world. Hypothermia is the first-line treatment, but the risk of death and long-term neurodevelopmental impairment remains still high. Allopurinol, a xantine-oxidase inhibitor, reduces the production of oxygen radicals and may have a synergic action with hypothermia as shown in animal models. This European funded study aims to evaluate the efficacy and safety of Allopurinol in infants with hypoxic-ischemic encephalopathy.
Materials and Methods: The study is a blinded randomized placebo-controlled parallel group multicenter trial (around 60 centers of 12 countries in Europe are involved). Allopurinol or placebo (Mannitol) will be administered intravenously immediately after birth and 24 hours later and standard care (including hypothermia) will be started. The sample size necessary for the statistical power consists of 846 neonates. The study will evaluate the efficacy of Allopurinol in terms of reduction of death or severe neurodevelopmental impairment at 24 months of age.
Conclusion: Our project is the first study testing the activity of Allopurinol in human neonates. Recruitment of patients will took place in the first months of this year and the full trial will past 5 years. The major concern is the large patient’s sample which can be reached only involving a wide number of neonatal nurseries. At present time, 13 Italian neonatal units has been recruited.
Keywords: hypoxic-ischemic encephalopathy, allopurinol, hypothermia, neurodevelopmental outcome
