The UNBLOCK Study: Utilization of Bivalirudin On Clots in Kids
Condition: Deep Venous Thrombosis
MeSH terms: Thrombosis; Venous Thrombosis
Study type: Interventional
Phase: Phase 1

Summary: 
      Thrombosis is a significant medical complication in children with chronic diseases. The
      currently utilized treatments have many drawbacks which can lead to poor outcomes. More
      modern therapies are available but have not been systematically tested in children. This
      study will determine whether one such medication, bivalirudin is a safer and more effective
      alterative.

      This study will monitor what effects the drug has upon the child's body and how the body
      processes the study drug (absorption, metabolism and elimination). The study will also
      evaluate the drug's effectiveness by following how long it takes to dissolve the clot. The
      safety issues being monitored relate to any observations of major or minor bleeding episodes
      after taking the drug, and/or any other side effects.
    

Detailed description: 
      This will be an open-label, single-arm, dose-finding, pharmacokinetic, safety and efficacy
      study of bivalirudin in children 6 months to 18 years of age with deep vein thrombosis. The
      specific aims are as follows:

        1. Pharmacodynamic analysis based on the activated partial thromboplastin time (aPTT) will
           be performed and the best bolus dose and initial infusion dose of bivalirudin will be
           determined for 3 age cohorts of children.

        2. Pharmacokinetic analysis of bivalirudin will be determined based on bivalirudin plasma
           levels in the same 3 age cohorts.

        3. Comparison of pharmacokinetics with pharmacodynamics will be performed to determine
           whether the aPTT is an adequate surrogate for plasma bivalirudin levels.

        4. The rate of clot resolution within 48-72 hours will be determined.

        5. The safety of bivalirudin will be determined by assessing for major and minor bleeding
           and other adverse events.

      A total of 30 patients will be enrolled in this study. They will be divided into 3 groups
      according to their age range (6 months-age to > 5, 5 to > 12 years and 12 to >18 years). The
      patient must have a deep vein thrombosis (clot in an artery or vein) that has been seen on an
      imaging test. After receiving the study drug, the subjects will then have blood tests at
      specific timepoints to measure how the drug is effecting the body and how the drug is acting
      once it is in the body. Based upon the levels of the blood tests, the dose of the study drug
      may be adjusted or stopped. The subject will continue on the drug until the clot is
      dissolved, the subject is prescribed a different anticoagulant or the physician or parents
      decide to remove the child off of the study. The drug will also be discontinued if any
      excessive bleeding or severe side effects related to the drug are observed. A follow up
      imaging study will be performed on all patients 48-72 hours after the drug was started. If
      the clot is still present at this time, another imaging study will be done at 30 days after
      the drug was given. The subjects will continue to have lab tests twice weekly for about 3
      weeks to monitor for the effects of the drug. After completion of the study, the patient will
      undergo a study exit physical exam between 20-40 days after the drug was stopped.
    

Intervention name(s): Bivalirudin
Intervention type(s): Drug
Intervention description(s): The initial bolus dose will be 0.125 mg/kg followed immediately by a continuous infusion of 0.125 mg/kg/hour.
Other intervention name(s): Angiomax
Intervention MeSH terms: Bivalirudin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: DVT; Deep Venous Thrombosis; UNBLOCK; Bivalirudin; Angiomax