The UNBLOCK Study: Utilization of Bivalirudin On Clots in Kids

This study has been completed.
Sponsor:
Collaborators:
Texas Children's Hospital
Children's Hospital Colorado
Children's Hospital of Philadelphia
Nationwide Children's Hospital
University of Texas Southwestern Medical Center
Information provided by (Responsible Party):
Guy Young, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:
NCT00812370
First received: December 18, 2008
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Deep Venous Thrombosis
Drug: Bivalirudin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Dose-finding, Pharmacokinetic, Safety and Efficacy Study of Bivalirudin in Children Between 6 Months and 18 Years of Age

Resource links provided by NLM:


Further study details as provided by Children's Hospital Los Angeles:

Primary Outcome Measures:
  • The study will assess efficacy by re-evaluating thrombus at 48-72 hours as well as continued efficacy by re-evaluating the thrombus at ~30 days after study drug initiation. [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics (PK) will also be assessed by measuring plasma bivalirudin levels and correlation of the PD to the PK parameter will be performed. The study will also assess safety by evaluating for bleeding, as well as other adverse events. [ Time Frame: twice a week until drug discontinuation ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: September 2008
Study Completion Date: July 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Bivalirudin
    The initial bolus dose will be 0.125 mg/kg followed immediately by a continuous infusion of 0.125 mg/kg/hour.
    Other Name: Angiomax
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.

  Eligibility

Ages Eligible for Study:   6 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children > 6 months to < 18 years of age.
  • Deep vein thrombosis demonstrated by objective testing (Duplex ultrasonography, venography, CT venography, MR venography, echocardiography). This imaging must be performed within 72 hours prior to initiation of study drug if no other anticoagulation has been started. If receiving other anticoagulation prior to start of study drug, imaging must be performed within 24 hours of study drug initiation.
  • Informed consent and assent from parent/guardian/patient

Exclusion Criteria:

  • Treatment of present thrombus with thrombolytic agent.
  • Treatment of present thrombus with another anticoagulant for more than 48 hours (low dose heparin for maintenance of venous or arterial catheter patency is allowed).
  • Baseline prothrombin time (PT) which is more than 3 seconds above the upper limit of normal or baseline activated partial thromboplastin time (aPTT) which is more than 5 seconds above the upper limit of normal.
  • Creatinine which is more than 20% above the upper limit of normal for age.
  • Presence of a known bleeding disorder.
  • Active bleeding.
  • Planned invasive procedure within 3 days.
  • Known pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00812370

Locations
United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, Colorado
UCD Hemophilia & Thrombosis Center
Aurora, Colorado, United States, 80045
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 432005
United States, Pennsylvania
The Childrens Hospital of Philidelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390
Baylor College of Medicine/Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Children's Hospital Los Angeles
Texas Children's Hospital
Children's Hospital Colorado
Children's Hospital of Philadelphia
Nationwide Children's Hospital
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Guy A Young, MD CHLA
  More Information

No publications provided

Responsible Party: Guy Young, Director, Hemostasis and Thrombosis Center, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT00812370     History of Changes
Other Study ID Numbers: 3070850
Study First Received: December 18, 2008
Last Updated: July 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital Los Angeles:
DVT
Deep Venous Thrombosis
UNBLOCK
Bivalirudin
Angiomax

Additional relevant MeSH terms:
Thrombosis
Venous Thrombosis
Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thromboembolism
Bivalirudin
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anticoagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014