Verslagen

Samenvatting van de aanvraag

Samenvatting
Dit item is dichtgeklapt
Dit item is opengeklapt

INTRODUCTION

Brain injury is a fundamental problem in duct-dependent congenital heart disease (DDCHD) neonates. Significant motor and cognitive problems are the result of early postnatally (after birth) and perioperatively (around cardiac surgery with cardiopulmonary bypass) induced brain injury. Allopurinol has the potential to reduce hypoxic-ischemic brain injury, is cardioprotective and safe.

 

AIM

Primary aim is to significantly reduce hypoxic-ischemic brain injury. Secondary aims are to improve brain and cardiac function and neurodevelopment.

 

DESIGN

A phase III, randomized, blinded, placebo-controlled, multicenter study. All 4 Dutch pediatric cardiothoracic surgery centers (Utrecht, Groningen, Rotterdam, Amsterdam/Leiden) will participate.

 

POPULATION

Neonates with a prenatally (before birth) or postnatally diagnosed DDCHD requiring cardiac surgery with cardiopulmonary bypass, including univentricular heart physiology, transposition of the great arteries and aortic arch anomalies.

 

INTERVENTION

Allopurinol or placebo 20 mg/kg i.v. early postnatally and perioperatively.

 

OUTCOMES

Primary outcome is a composite endpoint of hypoxic-ischemic brain injury on postoperative MRI or too instable for postoperative MRI or mortality. Secondary outcomes are brain and cardiac function and neurodevelopment.

 

PROCEDURES

Neuroimaging (MRI), neuromonitoring (aEEG, NIRS), neurodevelopment (GMs, Bayley-III-NL, executive functions), cardiac imaging (echo, MRI), biomarkers (cerebral, cardiac, inflammatory).

 

ANALYSIS

Group sequential primary analysis with equally spaced interim analysis for the prenatal diagnosis group, with the option to stop for efficacy/futility. Secondary analysis for the postnatal diagnosis group.

 

SAMPLE SIZE

208 patients (168 prenatal + 40 postnatal) are needed to reduce the primary outcome with 20% (one-sided alpha 5%, power 80%).

 

ECONOMIC EVALUATION

Allopurinol costs are low and a small reduction in hypoxic-ischemic brain injury will make this intervention very cost-effective.

Naar boven
Direct naar: InhoudDirect naar: NavigatieDirect naar: Onderkant website