Antenatal Allopurinol During Fetal Hypoxia

Conditions

Fetal Hypoxia, Reperfusion Injury

Keywords

allopurinol, neuroprotection, reperfusion injury, fetal hypoxia, post hypoxic-ischemic reperfusion damage

Brief summary

A former study (submitted) in 32 severely asphyxiated infants participating in a randomized double blind study, in which early postnatal allopurinol or a placebo (within 4 hours after birth) was administered to reduce free radical formation and consequently reperfusion/reoxygenation injury to the newborn brain, showed an unaltered high mortality and no clinically relevant improvement in morbidity in infants treated with allopurinol. It was hypothesized that postnatal allopurinol treatment started too late to reduce reperfusion-induced free radical surge and that initiating allopurinol treatment of the fetus with (imminent) hypoxia already via the mother during labor will be more effective to reduce free radical-induced post-asphyxial brain damage.

Job Klumper, Joepe J. Kaandorp, Ewoud Schuit, Floris Groenendaal, Corine Koopman-Esseboom et al. (13 authors)

PLoS ONE2018-08-2315 citations

10.1371/journal.pone.0201063

Maternal allopurinol administration during suspected fetal hypoxia: a novel neuroprotective intervention? A multicentre randomised placebo controlled trial

Joepe J. Kaandorp, Manon J.N.L. Benders, Ewoud Schuit, Carin M. A. Rademaker, Martijn A. Oudijk et al. (28 authors)

Archives of Disease in Childhood Fetal & Neonatal2014-12-1560 citations

10.1136/archdischild-2014-306769

Rapid target allopurinol concentrations in the hypoxic fetus after maternal administration during labour

Joepe J. Kaandorp, Marcel P. H. van den Broek, Manon J.N.L. Benders, Martijn A. Oudijk, Martina Porath et al. (16 authors)

Archives of Disease in Childhood Fetal & Neonatal2013-12-1821 citations

10.1136/archdischild-2013-304876

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

Kaandorp JJ, Benders MJ, Rademaker CM, Torrance HL, Oudijk MA, de Haan TR, Bloemenkamp KW, Rijken M, van Pampus MG, Bos AF, Porath MM, Oetomo SB, Willekes C, Gavilanes AW, Wouters MG, van Elburg RM, Huisjes AJ, Bakker SC, van Meir CA, von Lindern J, Boon J, de Boer IP, Rijnders RJ, Jacobs CJ, Uiterwaal CS, Mol BW, Visser GH, van Bel F, Derks JB.

2010-02-1849 citations

10.1186/1471-2393-10-8

Interventions

DRUGAllopurinol sodium

Allopurinol sodium 500 mg / 50 mL, intravenously, single dose

DRUGMannitol

Mannitol 500 mg/50 mL water for injection, intravenously, single dose

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Healthy volunteers

No

Inclusion criteria

* Gestational age of 36 weeks or more * Non-reassuring CTG, significant events on the STAN-monitor AND/OR FBS \< 7.20

Exclusion criteria

* Chromosomal abnormalities

Design outcomes

Primary

Measure	Time frame
Free radical production and markers of neuronal damage	Up to 24 hours postpartum

Secondary

Measure	Time frame
Developmental outcome	Up to 5 years of age
Mortality	Up to 28 days postpartum
Severe composite morbidity	Up to 28 days postpartum

Countries

Netherlands

Outcome results

None listed