Clinical trial NCT00412464: Pilot Dose Finding and Pharmacokinetic Study of Fondaparinux in Children With Thrombosis
Official title: A Pilot Dose-finding and Pharmacokinetic Study of Fondaparinux in Children With Deep Vein Thrombosis or Heparin-induced Thrombocytopenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Thrombosis
Heparin-induced Thrombocytopenia
Keywords: fondaparinux
thrombosis
heparin-induced thrombocytopenia
pediatrics
Lead sponsor: FDA Office of Orphan Products Development
Sponsor class: FED
First posted: 2006-12-18
Enrollment: 24
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Children between 1 year and 18 years of age.
* The presence of documented venous or arterial thrombosis confirmed by diagnostic imaging.
* Weight greater than 8.3 kg.
* Signed informed consent/assent.

Exclusion Criteria:

* Patients with active bleeding.
* Patients with planned invasive procedures less than 2 weeks from the time of enrollment.
* Patients with a contraindication to anticoagulation.
* Patients receiving thrombolytic agents.
* Patients with an INR\>1.5 or an activated partial thromboplastin time (PTT)\>40 seconds.
* Patients with a creatinine level above 1.2 times the upper limit of normal expected for age.
* Children \<1 year of age.

Primary outcomes:
measure: Number of Abnormal Lab Results Resulting in Adverse Events.
timeFrame: Study period which was up to 21 days of fondaparinux
measure: Therapeutic Plasma Concentration of Fondaparinux at 21 Days
timeFrame: 21 days
measure: Bleeding Events
timeFrame: Study period which was up to 21 days of fondaparinux
measure: Adverse Events
timeFrame: Study period which was up to 21 days of fondaparinux
measure: Thrombocytopenic Events
timeFrame: Study period which was up to 21 days of fondaparinux
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
Study officials:
affiliation: Children's Hospital of Orange County
name: Guy Young, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Young G, Yee FL, Khanna R, O'Brien D, Nugent DJ. Fondaparinux for the Treatment of Thrombosis in Children: A Prospective, Dose-Finding, Pharmacodynamic and Safety Study. Blood (ASH Annual Meeting Abstracts), Nov 2009; 114: 3130.
citation: Young G, Yee DL, O'Brien SH, Khanna R, Barbour A, Nugent DJ. FondaKIDS: a prospective pharmacokinetic and safety study of fondaparinux in children between 1 and 18 years of age. Pediatr Blood Cancer. 2011 Dec 1;57(6):1049-54. doi: 10.1002/pbc.23011. Epub 2011 Feb 11.