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

被引：57

作者：

Kaandorp, Joepe J. ^{[1
]}

Benders, Manon J. N. L. ^{[1
]}

Rademaker, Carin M. A. ^{[2
]}

Torrance, Helen L. ^{[1
]}

Oudijk, Martijn A. ^{[3
]}

de Haan, Timo R. ^{[4
]}

Bloemenkamp, Kitty W. M. ^{[5
]}

Rijken, Monique ^{[6
]}

van Pampus, Maria G. ^{[7
]}

Bos, Arie F. ^{[8
]}

Porath, Martina M. ^{[9
]}

Oetomo, Sidarto Bambang ^{[10
]}

Willekes, Christine ^{[11
]}

Gavilanes, A. W. Danilo ^{[12
]}

Wouters, Maurice G. A. J. ^{[13
]}

van Elburg, Ruurd M. ^{[14
]}

Huisjes, Anjoke J. M. ^{[15
]}

Bakker, Saskia C. M. J. E. R. ^{[16
]}

van Meir, Claudia A. ^{[17
]}

von Lindern, Jeannette ^{[18
]}

Boon, Janine ^{[19
]}

de Boer, Inge P. ^{[20
]}

Rijnders, Robbert J. P. ^{[21
]}

Jacobs, Corrie J. W. F. M. ^{[22
]}

Uiterwaal, Cuno S. P. M. ^{[23
]}

Mol, Ben Willem J. ^{[3
]}

Visser, Gerard H. A. ^{[1
]}

van Bel, Frank ^{[1
]}

Derks, Jan B. ^{[1
]}

机构：

[1] Univ Med Ctr, Perinatal Ctr, Utrecht, Netherlands

[2] Univ Med Ctr, Dept Clin Pharm, Utrecht, Netherlands

[3] Univ Amsterdam, Acad Med Ctr, Dept Obstet & Gynaecol, NL-1105 AZ Amsterdam, Netherlands

[4] Univ Amsterdam, Acad Med Ctr, Dept Neonatol, NL-1105 AZ Amsterdam, Netherlands

[5] Leiden Univ Med Ctr, Dept Obstet & Gynaecol, Leiden, Netherlands

[6] Leiden Univ Med Ctr, Dept Neonatol, Leiden, Netherlands

[7] Univ Groningen, Univ Med Ctr Groningen, Dept Obstet & Gynaecol, NL-9713 AV Groningen, Netherlands

[8] Univ Med Ctr Groningen, Dept Neonatol, NL-9713 AV Groningen, Netherlands

[9] Maxima Med Ctr, Dept Obstet & Gynaecol, Veldhoven, Netherlands

[10] Maxima Med Ctr, Dept Neonatol, Veldhoven, Netherlands

[11] Maastricht Univ Med Ctr, Dept Obstet & Gynaecol, Maastricht, Netherlands

[12] Maastricht Univ Med Ctr, Dept Neonatol, Maastricht, Netherlands

[13] Vrije Univ Amsterdam Med Ctr, Dept Obstet & Gynaecol, Amsterdam, Netherlands

[14] Vrije Univ Amsterdam Med Ctr, Dept Neonatol, Amsterdam, Netherlands

[15] Gelre Hosp, Dept Obstet & Gynaecol, Apeldoorn, Netherlands

[16] Gelre Hosp, Dept Paediat, Apeldoorn, Netherlands

[17] Groene Hart Hosp, Dept Obstet & Gynaecol, Gouda, Netherlands

[18] Groene Hart Hosp, Dept Paediat, Gouda, Netherlands

[19] Diakonessen Hosp, Dept Obstet & Gynaecol, Utrecht, Netherlands

[20] Diakonessen Hosp, Dept Paediat, Utrecht, Netherlands

[21] Jeroen Bosch Hosp, Dept Obstet & Gynaecol, sHertogenbosch, Netherlands

[22] Jeroen Bosch Hosp, Dept Paediat, sHertogenbosch, Netherlands

[23] Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

来源：

BMC PREGNANCY AND CHILDBIRTH | 2010年 / 10卷

关键词：

NEONATAL ENCEPHALOPATHY; PERINATAL ASPHYXIA; REPERFUSION INJURY; ISCHEMIC BRAIN; BLOOD-LEVELS; PHARMACOKINETICS; NEWBORNS;

D O I：

10.1186/1471-2393-10-8

中图分类号：

R71 [妇产科学];

学科分类号：

100211 ;

摘要：

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-test(2)-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.

引用

页数：6

共 25 条

[1]

[Anonymous], SUMMARY PRODUCT CHAR

[2] Early postnatal allopurinol does not improve short term outcome after severe birth asphyxia [J].