- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00412464
Pilot Dose Finding and Pharmacokinetic Study of Fondaparinux in Children With Thrombosis
April 14, 2015 updated by: Children's Hospital Los Angeles
A Pilot Dose-finding and Pharmacokinetic Study of Fondaparinux in Children With Deep Vein Thrombosis or Heparin-induced Thrombocytopenia
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Los Angeles, California, United States, 90027
- Children's Hospital Los Angeles
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Orange, California, United States, 92868
- Children's Hospital of Orange County
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Ohio
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Columbus, Ohio, United States, 43205
- Nationwide Children's Hospital
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Texas
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Houston, Texas, United States, 77030
- Texas Children's Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 year to 18 years (ADULT, CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Abnormal Lab Results Resulting in Adverse Events.
Time Frame: Study period which was up to 21 days of fondaparinux
|
The primary outcome measure was assessment of safety by reporting the number of abnormal lab results resulting in adverse events.
Safety laboratory assessments are as follows: Liver and kidney toxicity will be determined by serial measurements of AST, ALT, total bilirubin, BUN and creatinine.
Hematologic toxicity will be assessed by serial CBCs.
|
Study period which was up to 21 days of fondaparinux
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Therapeutic Plasma Concentration of Fondaparinux at 21 Days
Time Frame: 21 days
|
Subjects all had detailed pharmacokinetic measurements done which were subsequently analyzed in a population pharmacokinetic model.
This model then informed the dosing recommendations that were published as a result of the study.
|
21 days
|
Bleeding Events
Time Frame: Study period which was up to 21 days of fondaparinux
|
Bleeding assessment Patients will be monitored for bleeding symptoms by physician and nursing assessment.
Major bleeding will be defined as bleeding which is in a critical space (intracranial, retroperitoneal, or visceral) or leads to the need for blood transfusion.
Minor bleeding will be all other bleeding and will be classified as clinically significant (i.e.
If the physician has to take action to treat the minor bleed) or clinically insignificant (i.e. if the physician does not need to intervene to treat the minor bleed).
|
Study period which was up to 21 days of fondaparinux
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Adverse Events
Time Frame: Study period which was up to 21 days of fondaparinux
|
Adverse events will be defined as any untoward or unexpected event which can be a symptom, physical exam sign or laboratory abnormality.
Adverse events will be classified as serious if they lead to prolonged hospitalization, re-hospitalization, transfer to an intensive care unit, or death.
Adverse events will be categorized in terms of their likely association with fondaparinux as probably related, possibly related, unrelated, or unknown, and will be recorded according to standard adverse reporting guidelines for clinical trials.
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Study period which was up to 21 days of fondaparinux
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Thrombocytopenic Events
Time Frame: Study period which was up to 21 days of fondaparinux
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Patient's platelet counts should be kept above 50 x 10^9/L while on study with platelet transfusions as needed with the exception of patients enrolled under the HIT/ suspicion of HIT inclusion (platelet transfusions are contraindicated in HIT).
With regards to study patients who experience progressive decreases in platelet count to below 50 x 10^9/L while receiving fondaparinux (excluding patients being treated for HIT or suspicion of HIT), fondaparinux will be discontinued.
|
Study period which was up to 21 days of fondaparinux
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Guy Young, MD, Children's Hospital of Orange County
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2006
Primary Completion (ACTUAL)
June 1, 2009
Study Completion (ACTUAL)
December 1, 2009
Study Registration Dates
First Submitted
December 15, 2006
First Submitted That Met QC Criteria
December 15, 2006
First Posted (ESTIMATE)
December 18, 2006
Study Record Updates
Last Update Posted (ESTIMATE)
April 15, 2015
Last Update Submitted That Met QC Criteria
April 14, 2015
Last Verified
October 1, 2011
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Hematologic Diseases
- Embolism and Thrombosis
- Blood Platelet Disorders
- Thrombosis
- Thrombocytopenia
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Protease Inhibitors
- Factor Xa Inhibitors
- Antithrombins
- Serine Proteinase Inhibitors
- Anticoagulants
- Fondaparinux
- PENTA
Other Study ID Numbers
- 3091
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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