Official Title: “Does Antenatal Allopurinol Administration Improve Maternal and Neonatal Outcome in Intrauterine Growth Restriction?”

Growth retardation in utero may be caused by uteroplacental vascular insufficiency. When Doppler ultrasound studies of the umbilical artery are abnormal pathological intrauterine growth restriction (IUGR) can be diagnosed. IUGR fetuses have a higher mortality and morbidity, both perinatally and on the longer term. This is probably due to chronic malnourishment and hypoxia due to placental insufficiency. This placental dysfunction causes generation of harmful free oxygen radicals in the fetus. The IUGR fetus has a diminished antioxidative capacity which means these free radicals cannot be buffered sufficiently. This leads to fetal oxidative stress.

Previous studies have shown that allopurinol can inhibit the cascades that lead to generation of free radicals. High dosed allopurinol also scavenges radicals and binds free iron without adverse effects on the fetus or mother.

As IUGR is associated with placental insufficiency and excessive production of free radicals we hypothesize that antenatal allopurinol administration could lead to a decrease in oxidative stress in the mother and fetus and subsequent improvement of the maternal and/or neonatal outcome.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Intervention(s) in this Clinical Trial

• Drug: Allopurinol

Primary Measures

• free radical production / oxidative stress

Secondary Measures

• foetal parameters (Doppler, cardiotocography)
• postponement of birth
• morbidity (including long term neurodevelopmental outcome)
• mortality
• pharmacokinetices

Inclusion Criteria:

Mothers with a gestational age (GA) of 30 to 36 weeks with:

• Foetal growth retardation (growth <10th percentile) and
• Abnormal Doppler flow in the umbilical cord (umbilical artery pulsatility index (PI)>95th percentile)

Exclusion Criteria:

• Congenital, chromosomal or syndromal abnormalities
• Positive screening for intrauterine viral infections
• Mothers with gout and high uric acid
• creatinine > 100 umol/l
• ASAT > 80 U/l, ALAT > 80 U/l
• Uric acid > 0,50 mmol/l

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: UMC Utrecht

Overall Clinical Trial Officials and Contacts

Frank van Bel, Prof MD, PhD Study Director Wilhelmina Children's Hospital / UMC Utrecht  

Overall Contact: Manon Benders, MD, PhD 0031 30 2504545 m.benders@umcutrecht.nl

Information obtained from ClinicalTrials.gov on August 08, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00346463

Study ID Number: METC UMCU 05-207K

ClinicalTrials.gov Identifier: NCT00346463

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)