Antenatal Allopurinol During Fetal Hypoxia

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Fetal Hypoxia; Reperfusion Injury	Drug: Allopurinol sodium; Drug: Mannitol	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	222 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Does Antenatal Allopurinol Administration Reduce Post-hypoxic-ischemic Reperfusion Damage During Fetal Hypoxia in the Newborn?
Study Start Date :	October 2009
Actual Primary Completion Date :	December 2011
Estimated Study Completion Date :	December 2016

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Allopurinol; 500 mg allopurinol/ 50 mL water for injection intravenously	Drug: Allopurinol sodium; Allopurinol sodium 500 mg / 50 mL, intravenously, single dose; Other Name: Acepurin
Placebo Comparator: Placebo; 500 mg mannitol/50 mL water for injection intravenously	Drug: Mannitol; Mannitol 500 mg/50 mL water for injection, intravenously, single dose

Outcome Measures

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Primary Outcome Measures :

1. Free radical production and markers of neuronal damage [ Time Frame: Up to 24 hours postpartum ]

Secondary Outcome Measures :

1. Developmental outcome [ Time Frame: Up to 5 years of age ]
2. Mortality [ Time Frame: Up to 28 days postpartum ]
3. Severe composite morbidity [ Time Frame: Up to 28 days postpartum ]

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Netherlands
AMC
Amsterdam, Netherlands
VUmc
Amsterdam, Netherlands
Gelre hospitals
Apeldoorn, Netherlands
Jeroen Bosch Hospital
Den Bosch, Netherlands
Groene Hart Hospital
Gouda, Netherlands
UMCG
Groningen, Netherlands
LUMC
Leiden, Netherlands
Maastricht University Medical Center
Maastricht, Netherlands
Wilhelmina Children's Hospital/UMC Utrecht
Utrecht, Netherlands, 3508AB
Diakonessenhuis
Utrecht, Netherlands
Maxima Medical Center
Veldhoven, Netherlands

Sponsors and Collaborators

UMC Utrecht

ZonMw: The Netherlands Organisation for Health Research and Development

Investigators

Study Director:	Frank van Bel, Prof MD PhD	Wilhelmina Children's Hospital/UMC Utrecht
Principal Investigator:	Manon JN Benders, MD, PhD	UMC Utrecht
Principal Investigator:	Jan B Derks, MD, PhD	UMC Utrecht
Principal Investigator:	Joepe J Kaandorp, MD	UMC Utrecht
Principal Investigator:	Gerard H Visser, MD, PhD	UMC Utrecht
Principal Investigator:	Ben WJ Mol, MD, PhD	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Principal Investigator:	Carin MA Rademaker, PhD	Clinical Pharmacy, UMCU

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

website allo-trial 

Publications:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

Responsible Party:	dr. M.J.N.L. Benders, MD, PhD, UMC Utrecht
ClinicalTrials.gov Identifier:	NCT00189007 History of Changes
Other Study ID Numbers:	ZonMw 170991001; ALLO-trial ( Other Identifier: Dutch Consortium for Studies in Obstetrics and Gynaecology ); 2006-005796-18 ( EudraCT Number ); 170991001 ( Other Grant/Funding Number: ZonMw ); NTR-1383 ( Registry Identifier: Dutch Trial Register ); NL26516.000.09 ( Other Identifier: The Central Committee on Research Involving Human Subjects (CCMO) )
First Posted:	September 16, 2005
Last Update Posted:	March 29, 2012
Last Verified:	March 2012

Keywords provided by dr. M.J.N.L. Benders, UMC Utrecht:

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

Additional relevant MeSH terms:

Hypoxia; Reperfusion Injury; Fetal Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Fetal Diseases; Pregnancy Complications; Allopurinol; Mannitol	Antimetabolites; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gout Suppressants; Antirheumatic Agents; Free Radical Scavengers; Antioxidants; Protective Agents; Physiological Effects of Drugs; Diuretics, Osmotic; Diuretics; Natriuretic Agents