Effect of Allopurinol for Hypoxic-ischemic Brain Injury on Neurocognitive Outcome

• Status: Recruiting
• Trial end date: 2025-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of death or long-term disability in infants born at term in the western world, affecting about 1-4 per 1.000 life births and consequently about 5-20.000 infants per year in Europe.

Hypothermic treatment became the only established therapy to improve outcome after perinatal hypoxic-ischemic insults. Despite hypothermia and neonatal intensive care, 45-50% of affected children die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective interventions, beside hypothermia, are warranted to further improve their outcome.

Allopurinol is a xanthine oxidase inhibitor and reduces the production of oxygen radicals and brain damage in experimental, animal, and early human studies of ischemia and reperfusion.

This project aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to near-term infants with HIE in addition to hypothermic treatment.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Tuebingen
• Collaborators: ACE Pharmaceuticals BV; Fundación para la Investigación del Hospital Clínico de Valencia; Helsingin Ja Uudenmaan Sairaanhoitopiirin; Helsinki University; Katholieke Universiteit Leuven; KU Leuven; Oslo University Hospital; Poznan University of Medical Sciences; Tartu University Hospital; Technische Universität Dresden; UMC Utrecht; Universidade do Porto; Università degli Studi di Udine; University Hospital Ostrava; University of Helsinki; University of Vienna; University of Zurich
• Treatments: Allopurinol; Mannitol

Criteria

Inclusion criteria

Term and near-term infants with a history of disturbed labour who meet at least one criterion of perinatal acidosis (or ongoing resuscitation) and at least two early clinical signs of potentially evolving encephalopathy as defined herein:

Severe perinatal metabolic acidosis or ongoing cardiopulmonary resuscitation at 5 min after birth:

At least 1 out of the following 5 criteria must be met

• Umbilical (or arterial or reliable venous) blood gas within 30 min after birth with pH<7.0

• Umbilical (or arterial or reliable venous) blood gas within 30 min after birth with base deficit ≥16 mmol/l

• Need for ongoing cardiac massage at/beyond 5 min postnatally

• Need for adrenalin administration during resuscitation

• APGAR score ≤5 at 10min AND

Early clinical signs of potentially evolving encephalopathy:

At least 2 out of the following 4 criteria must be met:

• Altered state of consciousness (reduced or absent response to stimulation or hyperexcitability)

• Severe muscular hypotonia or hypertonia,

• Absent or insufficient spontaneous respiration (e.g., gasping only) with need for respiratory support at 10 min postnatally

• Abnormal primitive reflexes (absent suck or gag or corneal or Moro reflex) or abnormal movements (e.g., potential clinical correlates of seizure activity)

Exclusion criteria

• gestational age below 36 weeks

• birth weight below 2500 g

• postnatal age >30min at the end of screening phase

• severe congenital malformation or syndrome requiring neonatal surgery or affecting long-term outcome

• patient considered "moribund" / "non-viable" (e.g., lack of spontaneous cardiac activity and ongoing chest compression at 30min)

• decision for "comfort care only" before study drug administration

• parents declined study participation as response to measures of community engagement

• both parents are insufficiently fluent in the study site's national language(s) or English or do not seem to have the intellectual capacity to understand the study procedures and to give consent as judged by the personnel who had been in contact with the mother/father before delivery.

• both parents/guardians less than 18 years of age, in case of single parent/guardian this one less than 18 years of age