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

NCT00412464 | Completed Phase 1 Results DMC

• 1 other identifier: 3091
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 4

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.

Conditions

Thrombosis; Heparin-induced Thrombocytopenia

Keywords

fondaparinux; thrombosis; heparin-induced thrombocytopenia; pediatrics

Outcome Measures

Primary Outcomes (5)

• Number of Abnormal Lab Results Resulting in Adverse Events.

  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

• Therapeutic Plasma Concentration of Fondaparinux at 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

  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

• Adverse Events

  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.

  Study period which was up to 21 days of fondaparinux

• Thrombocytopenic Events

  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

Interventions

Fondaparinux DRUG

Fondaparinux 0.1 mg/kg (up to 7.5 mg max initial dose) once daily for up to 21 days.

Also known as: Arixtra

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital Los Angeles: lead

Study Sites (4)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (2)

• 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.

  RESULT

• 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.

  PMID: 21319285 RESULT

MeSH Terms

Conditions

Thrombosis

Interventions

Fondaparinux

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Oligosaccharides; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Guy Young
• Organization: Children's Hospital Los Angeles

gyoung@chla.usc.edu

323-361-5507

Study Officials

• Guy Young, MD

  Children's Hospital of Orange County

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 15, 2006
• First Posted: December 18, 2006
• Study Start: September 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: December 1, 2009
• Last Updated: April 15, 2015
• Results First Posted: December 6, 2011

Record last verified: 2011-10

Locations

US (4)