Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study

BMC Pregnancy and Childbirth. 2010;10(1):8 DOI 10.1186/1471-2393-10-8

 

Journal Homepage

Journal Title: BMC Pregnancy and Childbirth

ISSN: 1471-2393 (Online)

Publisher: BMC

LCC Subject Category: Medicine: Gynecology and obstetrics

Country of publisher: United Kingdom

Language of fulltext: English

Full-text formats available: PDF, HTML

 

AUTHORS


von Lindern Jeannette

van Meir Claudia A

Bakker Saskia CMJER

Huisjes Anjoke JM

van Elburg Ruurd M

Wouters Maurice GAJ

Gavilanes AW Danilo

Willekes Christine

Oetomo Sidarto

Porath Martina M

Bos Arie F

van Pampus Maria G

Rijken Monique

Bloemenkamp Kitty WM

de Haan Timo R

Oudijk Martijn A

Torrance Helen L

Rademaker Carin MA

Benders Manon JNL

Kaandorp Joepe J

Boon Janine

de Boer Inge P

Rijnders Robbert JP

Jacobs Corrie JWFM

Uiterwaal Cuno SPM

Mol Ben Willem J

Visser Gerard HA

van Bel Frank

Derks Jan B

EDITORIAL INFORMATION

Open peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 21 weeks

 

Abstract | Full Text

<p>Abstract</p> <p>Background</p> <p>Hypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy.</p> <p>Methods/Design</p> <p>The proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia.</p> <p>Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20).</p> <p>Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated.</p> <p>We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test<sub>2-sided</sub>). Analysis will be by intention to treat and it allows for one interim analysis.</p> <p>Discussion</p> <p>In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia.</p> <p>Trial registration number</p> <p>Clinical Trials, protocol registration system: NCT00189007</p>