Peer-reviewed article
Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)
for the ALBINO Study Group, Christian A. Maiwald, Kim V. Annink, Mario Rüdiger, Manon J.N.L. Benders et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a study protocol for a large European clinical trial testing whether allopurinol, a drug that reduces oxygen-related damage, can improve outcomes when added to the standard cooling treatment for newborns with hypoxic-ischemic encephalopathy (brain damage from lack of oxygen). The trial will enroll term babies who show signs of evolving brain injury and measure whether allopurinol reduces death and severe neurodevelopmental disability by age two. The study combines the drug with therapeutic hypothermia, which is the only proven treatment available today for this serious condition affecting thousands of European infants annually.
Key points
- Hypoxic-ischemic encephalopathy affects up to 20,000 infants per year in Europe and causes significant death and long-term disability
- Therapeutic hypothermia is currently the only established therapy to improve outcomes in affected infants
- Allopurinol works by reducing oxygen radical production that contributes to secondary brain damage after oxygen restoration
- This is a Phase III double-blinded randomized placebo-controlled trial across multiple European centers
- Primary outcome is death or severe neurodevelopmental impairment versus survival without severe impairment at 24 months
Limitations
This document is a study protocol describing a planned trial, not results. It cannot tell us whether allopurinol actually works, what the safety profile is, or whether it will become standard care—these answers await completion and analysis of the trial.
Abstract
BACKGROUND: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. METHODS: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. DISCUSSION: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. TRIAL REGISTRATION: NCT03162653, www.ClinicalTrials.gov , May 22, 2017.