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
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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