Antenatal Allopurinol During Fetal Hypoxia

NCT00189007 | Unknown Phase 3 DMC

• 6 other identifiers: ZonMw 170991001ALLO-trial2006-005796-18170991001NTR-1383NL26516.000.09
• Study Type: interventional
• Target: 222
• Locations: 1 country
• Sites: 11

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.

Conditions

Fetal Hypoxia; Reperfusion Injury

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Free radical production and markers of neuronal damage

  Up to 24 hours postpartum

Secondary Outcomes (3)

• Developmental outcome

  Up to 5 years of age

• Mortality

  Up to 28 days postpartum

• Severe composite morbidity

  Up to 28 days postpartum

Study Arms (2)

Allopurinol

EXPERIMENTAL

500 mg allopurinol/ 50 mL water for injection intravenously

Drug: Allopurinol sodium

Placebo

PLACEBO COMPARATOR

500 mg mannitol/50 mL water for injection intravenously

Drug: Mannitol

Interventions

Allopurinol sodium DRUG

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

Also known as: Acepurin

Allopurinol

Mannitol DRUG

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

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Chromosomal abnormalities

Sponsors & Collaborators

• UMC Utrecht: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (11)

Wilhelmina Children's Hospital/UMC Utrecht

Utrecht, Utrecht, 3508AB, Netherlands

Location

Jeroen Bosch Hospital

's-Hertogenbosch, Netherlands

Location

AMC

Amsterdam, Netherlands

Location

VUmc

Amsterdam, Netherlands

Location

Gelre hospitals

Apeldoorn, Netherlands

Location

Groene Hart Hospital

Gouda, Netherlands

Location

UMCG

Groningen, Netherlands

Location

LUMC

Leiden, Netherlands

Location

Maastricht University Medical Center

Maastricht, Netherlands

Location

Diakonessenhuis

Utrecht, Netherlands

Location

Maxima Medical Center

Veldhoven, Netherlands

Location

Related Publications (5)

• 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.

  PMID: 20167117 BACKGROUND

• 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.

  PMID: 30138355 DERIVED

• 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.

  PMID: 25512466 DERIVED

• 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.

  PMID: 24352085 DERIVED

• 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.

  PMID: 19564319 DERIVED

MeSH Terms

Conditions

Fetal Hypoxia; Reperfusion Injury

Interventions

Allopurinol; Mannitol

Condition Hierarchy (Ancestors)

Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Officials

• Frank van Bel, Prof MD PhD

  Wilhelmina Children's Hospital/UMC Utrecht

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 11, 2005
• First Posted: September 16, 2005
• Study Start: October 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2016
• Last Updated: March 29, 2012

Record last verified: 2012-03

Locations

NL (11)