Cerebrum and Cardiac Protection With Allopurinol in Neonates With Critical Congenital Heart Disease Requiring Cardiac Surgery With Cardiopulmonary Bypass

Summary

Neurodevelopmental impairment due to delayed brain development and brain injury is a fundamental problem in children with critical congenital heart disease (CCHD). Significant longterm motor-, cognitive-, and behavioral problems are the result of early postnatally and perioperatively induced brain injury. Allopurinol, a xanthine oxidase inhibitor, prevents the formation of toxic free oxygen radicals, thereby limiting hypoxia-reperfusion damage. Both animal and neonatal studies suggest that administration of allopurinol reduces hypoxic-ischemic brain injury, is cardioprotective, and safe. This study aims to evaluate the efficacy and safety of allopurinol administered early postnatally and perioperatively in children with a CCHD requiring cardiac surgery with cardiopulmonary bypass.

Conditions

• Congenital Heart Disease in Children
• Neuroprotection

Interventions

DRUG

Allopurinol

Allopurinol powder for solution for infusion (PFI) 20 mg/kg body weight per administration will be administered early postnatally (within 45 minutes and 12 hours after the first dose), preoperatively (12 hours before surgery), intraoperatively (during surgery) and postoperatively (24 hours after surgery) to the neonate in case of a prenatal CCHD diagnosis. Allopurinol PFI will be administered only pre-, intra- and postoperatively to the neonate in case of a postnatal CCHD diagnosis.

DRUG

Mannitol

Mannitol powder for solution (PFI) placebo will be administered early postnatally (within 45 minutes and 12 hours after birth), preoperatively (12 hours before surgery), intraoperatively (during surgery), and postoperatively (24 hours after surgery) to the neonate in case of a prenatal CCHD diagnosis. Mannitol PFI-placebo will be administered only pre-, intra- and postoperatively to the neonate in case of a postnatal CCHD diagnosis.

Sponsors & Collaborators

• ZonMw: The Netherlands Organisation for Health Research and Development

  collaborator OTHER

• University Medical Center Groningen

  collaborator OTHER

• Erasmus Medical Center

  collaborator OTHER

• University Medical Center Nijmegen

  collaborator OTHER

• ACE Pharmaceuticals BV

  collaborator OTHER

• dr. M.J.N.L. Benders

  lead OTHER

Principal Investigators

• Manon JNL Benders, Prof. MD PhD · University Medical Center Utrecht (UMC Utrecht)

• Johannes (Hans) MPJ Breur, MD PhD · University Medical Center Utrecht (UMC Utrecht)

• Nicolaas (Koos) JG Jansen, MD PhD · University Medical Center Utrecht (UMC Utrecht)

• Raymond Stegeman, MD · University Medical Center Utrecht (UMC Utrecht)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Max Age

1 Month

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-02-14

Primary Completion

2026-10-31

Completion

2028-12-31

Countries

• Netherlands

Study Locations