Clinical trial NCT00189007: Antenatal Allopurinol During Fetal Hypoxia
Official title: Does Antenatal Allopurinol Administration Reduce Post-hypoxic-ischemic Reperfusion Damage During Fetal Hypoxia in the Newborn?
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Fetal Hypoxia
Reperfusion Injury
Keywords: allopurinol
neuroprotection
reperfusion injury
fetal hypoxia
post hypoxic-ischemic reperfusion damage
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2005-09-16
Enrollment: 222
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Free radical production and markers of neuronal damage
timeFrame: Up to 24 hours postpartum
Secondary outcomes:
measure: Developmental outcome
timeFrame: Up to 5 years of age
measure: Mortality
timeFrame: Up to 28 days postpartum
measure: Severe composite morbidity
timeFrame: Up to 28 days postpartum
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: AMC
city: Amsterdam
country: Netherlands
facility: VUmc
city: Apeldoorn
country: Netherlands
facility: Gelre hospitals
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Hospital
city: Gouda
country: Netherlands
facility: Groene Hart Hospital
city: Groningen
country: Netherlands
facility: UMCG
city: Leiden
country: Netherlands
facility: LUMC
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Utrecht
country: Netherlands
facility: Wilhelmina Children's Hospital/UMC Utrecht
city: Utrecht
country: Netherlands
facility: Diakonessenhuis
city: Veldhoven
country: Netherlands
facility: Maxima Medical Center
Study officials:
affiliation: Wilhelmina Children's Hospital/UMC Utrecht
name: Frank van Bel, Prof MD PhD
role: STUDY_DIRECTOR
affiliation: UMC Utrecht
name: Manon JN Benders, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UMC Utrecht
name: Jan B Derks, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UMC Utrecht
name: Joepe J Kaandorp, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UMC Utrecht
name: Gerard H Visser, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Ben WJ Mol, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Pharmacy, UMCU
name: Carin MA Rademaker, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study. BMC Pregnancy Childbirth. 2010 Feb 18;10:8. doi: 10.1186/1471-2393-10-8.
citation: Klumper J, Kaandorp JJ, Schuit E, Groenendaal F, Koopman-Esseboom C, Mulder EJH, Van Bel F, Benders MJNL, Mol BWJ, van Elburg RM, Bos AF, Derks JB; ALLO-trial study group. Behavioral and neurodevelopmental outcome of children after maternal allopurinol administration during suspected fetal hypoxia: 5-year follow up of the ALLO-trial. PLoS One. 2018 Aug 23;13(8):e0201063. doi: 10.1371/journal.pone.0201063. eCollection 2018.
citation: Kaandorp JJ, Benders MJ, Schuit E, Rademaker CM, Oudijk MA, Porath MM, Oetomo SB, Wouters MG, van Elburg RM, Franssen MT, Bos AF, de Haan TR, Boon J, de Boer IP, Rijnders RJ, Jacobs CJ, Scheepers LH, Gavilanes DA, Bloemenkamp KW, Rijken M, van Meir CA, von Lindern JS, Huisjes AJ, Bakker SC, Mol BW, Visser GH, Van Bel F, Derks JB. Maternal allopurinol administration during suspected fetal hypoxia: a novel neuroprotective intervention? A multicentre randomised placebo controlled trial. Arch Dis Child Fetal Neonatal Ed. 2015 May;100(3):F216-23. doi: 10.1136/archdischild-2014-306769. Epub 2014 Dec 15.
citation: Kaandorp JJ, van den Broek MP, Benders MJ, Oudijk MA, Porath MM, Bambang Oetomo S, Wouters MG, van Elburg R, Franssen MT, Bos AF, Mol BW, Visser GH, van Bel F, Rademaker CM, Derks JB; ALLO-trial Study Group. Rapid target allopurinol concentrations in the hypoxic fetus after maternal administration during labour. Arch Dis Child Fetal Neonatal Ed. 2014 Mar;99(2):F144-8. doi: 10.1136/archdischild-2013-304876. Epub 2013 Dec 18.
citation: Torrance HL, Benders MJ, Derks JB, Rademaker CM, Bos AF, Van Den Berg P, Longini M, Buonocore G, Venegas M, Baquero H, Visser GH, Van Bel F. Maternal allopurinol during fetal hypoxia lowers cord blood levels of the brain injury marker S-100B. Pediatrics. 2009 Jul;124(1):350-7. doi: 10.1542/peds.2008-2228.