Pilot Dose Finding and Pharmacokinetic Study of Fondaparinux in Children With Thrombosis

This clinical trial will assess the pharmacokinetics and safety of the novel anticoagulant,
fondaparinux sodium (Arixtra) in pediatric patients with thromboembolism. Currently
available anticoagulants have significant limitations especially as it applies to the
pediatric population. Thus novel agents with improved pharmacologic properties are needed to
improve the care of this increasingly recognized complication in children. Furthermore, the
only available agent for long-term anticoagulation in children with heparin-induced
thrombocytopenia is warfarin. Anticoagulation with warfarin in the pediatric population is
problematic due to its narrow therapeutic index and the numerous drug and food interactions
necessitating frequent laboratory monitoring. In addition, oral administration of warfarin
(which cannot be compounded to a liquid) is difficult in young children. Thus a novel agent
for this condition is needed and fondaparinux does not cross-react with heparin antibodies.
The aims of the study are to determine the proper dosing regimen (dose and interval) and
safety in patients less than 18 years of age with thrombosis or heparin-induced
thrombocytopenia. Another aim is to assess the utility of thromboelastography as a
monitoring tool for patients on fondaparinux. This will be a pilot study which will enroll
24 patients in 3 age cohorts. Patients will receive an initial dose of 0.1mg/kg
subcutaneoulsy daily. After the first dose, fondaparinux levels will be drawn at 2,4,12, and
24 hours after administration. Dose adjustments will be made based on the 4 hour (peak)
level and trough levels at 12 and 24 hours will determine if daily dosing is feasible.
Thromboelastography will be performed at 2 or 4 hours and 24 hours with the results
correlated with the plasma activity level. Safety will be assessed by physical examination,
laboratory testing, and if necessary diagnostic imaging to determine the incidence of minor
and major bleeding. Pharmacokinetic analyses as well as safety and efficacy determinations
will be made which will provide valuable information on this promising new anticoagulant for
pediatric patients.