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|Title:||Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study|
de Haan, T.
van Pampus, M.
Bambang Oetomo, S.
Danilo Gavilanes, A.
van Elburg, R.
van Meir, C.
von Lindern, J.
|Citation:||BMC Pregnancy and Childbirth, 2010; 10(1):8-1-8-6|
|Publisher:||BioMed Central Ltd.|
|Joepe J Kaandorp ... Ben Willem J Mol ... et al.|
|Abstract:||BACKGROUND 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. METHODS/DESIGN 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. 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). 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. 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-test2-sided). Analysis will be by intention to treat and it allows for one interim analysis. DISCUSSION In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia. TRIAL REGISTRATION NUMBER Clinical Trials, protocol registration system: NCT00189007|
|Keywords:||Humans; Hypoxia-Ischemia, Brain; Asphyxia Neonatorum; Allopurinol; Phosphopyruvate Hydratase; Xanthine Oxidase; Nerve Growth Factors; S100 Proteins; Free Radical Scavengers; Prenatal Care; Multivariate Analysis; Regression Analysis; Prospective Studies; Pilot Projects; Double-Blind Method; Pregnancy; Infant, Newborn; Netherlands; Female; Fetal Hypoxia; S100 Calcium Binding Protein beta Subunit; Biomarkers|
|Rights:||© 2010 Kaandorp et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.|
|Appears in Collections:||Paediatrics publications|
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