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

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.

Conditions

• Encephalopathy, Hypoxic-Ischemic
• Infant, Newborn, Diseases

Interventions

DRUG

Allopurinol

Allopurinol, powder for injection (PFI), administered in two doses. First dose (20 mg/kg in 2ml/kg sterile water for injection) given as soon as intravenous access is established and no later than 30min postnatally and second dose (10mg/kg in 1ml/kg sterile water for injection) 12 hours thereafter. The second dose will only be administered to in infants on therapeutic hypothermia. Infants who recover quickly and do not qualify for and hence do not undergo hypothermia will not receive a second dose. Administration will be by continuous infusion using a syringe pump over 10min through secure venous access.

DRUG

Mannitol

Placebo (Mannitol, PFI, 20mg/kg in the same volume and at the same time intervals as the intervention group - (2nd dose 10mg/kg only if infant undergoes therapeutic hypothermia)).

Sponsors & Collaborators

• Technische Universität Dresden

  collaborator OTHER

• UMC Utrecht

  collaborator OTHER

• KU Leuven

  collaborator OTHER

• University of Zurich

  collaborator OTHER

• University of Vienna

  collaborator OTHER

• Fundación para la Investigación del Hospital Clínico de Valencia

  collaborator OTHER

• Universidade do Porto

  collaborator OTHER

• Oslo University Hospital

  collaborator OTHER

• Università degli Studi di Udine

  collaborator UNKNOWN

• Helsingin Ja Uudenmaan Sairaanhoitopiirin

  collaborator UNKNOWN

• University of Helsinki

  collaborator OTHER

• Poznan University of Medical Sciences

  collaborator OTHER

• Tartu University Hospital

  collaborator OTHER

• ACE Pharmaceuticals BV

  collaborator OTHER

• University Hospital Tuebingen

  lead OTHER

Principal Investigators

• Axel Franz, Prof. Dr. · University Children's Hospital Tuebingen

• Rüdiger Mario, Prof. Dr. · University Children's Hospital Dresden

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Max Age

45 Minutes

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-03-25

Primary Completion

2026-01-31

Completion

2026-01-31

Countries

• Austria
• Belgium
• Estonia
• Finland
• Germany
• Italy
• Netherlands
• Norway
• Poland
• Portugal
• Spain
• Switzerland

Study Locations