Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study
Autor: | Monique Rijken, Timo R. de Haan, Saskia C. M. J. E. R. Bakker, Jan B. Derks, Joepe J. Kaandorp, Christine Willekes, Gerard H. A. Visser, Kitty W.M. Bloemenkamp, Jeannette S von Lindern, Arie Bos, Anjoke J.M. Huisjes, Robbert J.P. Rijnders, Martijn A. Oudijk, Janine Boon, Corrie J. W. F. M. Jacobs, Frank van Bel, Carin M. A. Rademaker, Helen L. Torrance, Maurice G.A.J. Wouters, A W Danilo Gavilanes, Ruurd M. van Elburg, Martina Porath, Claudia A. van Meir, Inge P. de Boer, Maria G. van Pampus, Manon J.N.L. Benders, Cuno S. P. M. Uiterwaal, Ben W.J. Mol, Sidarto Bambang Oetomo |
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Přispěvatelé: | Obstetrics and Gynaecology, Amsterdam Neuroscience, Other Research, Neonatology, Other departments, Amsterdam Public Health, Obstetrics and gynaecology, Pediatric surgery, ICaR - Ischemia and repair, Faculteit Medische Wetenschappen/UMCG, Reproductive Origins of Adult Health and Disease (ROAHD) |
Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
PHARMACOKINETICS
Pilot Projects law.invention Randomized controlled trial Pregnancy law Obstetrics and Gynaecology Medicine Prospective Studies REPERFUSION INJURY Netherlands Asphyxia Neonatorum NEWBORNS S100 Proteins Obstetrics and Gynecology Prenatal Care Free Radical Scavengers Anesthesia Hypoxia-Ischemia Brain Regression Analysis Female medicine.symptom medicine.drug Xanthine Oxidase Allopurinol Encephalopathy ISCHEMIC BRAIN S100 Calcium Binding Protein beta Subunit Fetal Hypoxia Placebo lcsh:Gynecology and obstetrics Double-Blind Method Study protocol Humans Nerve Growth Factors lcsh:RG1-991 Asphyxia PERINATAL ASPHYXIA business.industry Neonatal encephalopathy NEONATAL ENCEPHALOPATHY Infant Newborn Interim analysis medicine.disease Perinatal asphyxia BLOOD-LEVELS Phosphopyruvate Hydratase Multivariate Analysis business Biomarkers |
Zdroj: | Kaandorp, J J, Benders, M J N L, Rademaker, C M A, Torrance, H L, Oudijk, M A, Haan, T R, Bloemenkamp, K M, Rijken, M, van Pampus, M G, Bos, A F, Porath, M M, Oetomo, S B, Willekes, C, Gavilanes, A W D, Wouters, M G A J, van Elburg, R M, Huisjes, A J M, Bakker, S C M J, van Meir, C A, von Lindern, J, Boon, J, de Boer, I P, Rijnders, R J P, Jacobs, C W F, Uiterwaal, C S P M, Mol, B W J, Visser, G H A, van Bel, F & Derks, J B 2010, ' Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study ', BMC Pregnancy and Childbirth, vol. 10, pp. 8 . https://doi.org/10.1186/1471-2393-10-8 BMC Pregnancy and Childbirth, 10 BMC pregnancy and childbirth, 10(1). BioMed Central BMC Pregnancy and Childbirth BMC Pregnancy and Childbirth, Vol 10, Iss 1, p 8 (2010) BMC Pregnancy and Childbirth, 10. BioMed Central BMC Pregnancy and Childbirth, 10:8. BMC |
ISSN: | 1471-2393 |
Popis: | 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 |
Databáze: | OpenAIRE |
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