Pilot Dose Finding and Pharmacokinetic Study of Fondaparinux in Children With Thrombosis
Condition: Thrombosis; Heparin-induced Thrombocytopenia
MeSH terms: Thrombosis; Thrombocytopenia
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will evaluate the use of a blood thinner, fondaparinux, which is approved for use
      in adults (not in children) in a children aged 1-18 years. Subject with a blood clot
      (thrombosis) or heparin-induced thrombocytopenia who need to be on a blood thinner will be
      eligible to participate. Subjects will receive a once daily dose of fondaparinux followed by
      blood tests at 2, 4, 12, and 24 hours after the first dose in order to determine the proper
      dose for this age group. The hypothesis is that children receiving fondaparinux will be able
      to receive a once daily dose. The currently available alternative agent, enoxaparin, needs to
      be given twice daily. In addition, an evaluation of the safety of this medication will be
      made by assessing for side effects, especially bleeding.
    

Detailed description: 
      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 have a total of 24
      patients in 3 age cohorts with 8 patients per cohort as follows: 1-5 years, 6 -12 years, and
      12-18 years as the pharmacokinetics of medications differ by age. Patients will receive an
      initial dose of 0.1mg/kg subcutaneously 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.
    

Intervention name(s): Fondaparinux
Intervention type(s): Drug
Intervention description(s): Fondaparinux 0.1 mg/kg (up to 7.5 mg max initial dose) once daily for up to 21 days.
Other intervention name(s): Arixtra
Intervention MeSH terms: PENTA; Fondaparinux
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: fondaparinux; thrombosis; heparin-induced thrombocytopenia; pediatrics