Status:

COMPLETED

An Open-label, Randomized, Multicenter Phase IIIb Study to Assess the Efficacy, Safety and Tolerance of BERIPLEX® P/N (Kcentra) Compared With Plasma for Rapid Reversal of Coagulopathy Induced by Vitamin K Antagonists in Subjects Requiring an Urgent Surgical Procedure

Lead Sponsor:

CSL Behring

Conditions:

Reversal of Coagulopathy

Eligibility:

All Genders

18+ years

Phase:

PHASE3

Brief Summary

The purpose of this study is to evaluate efficacy, safety and tolerance of Beriplex® P/N (Kcentra) compared with plasma in regard to rapid reversal of coagulopathy induced by vitamin K antagonists in ...

Eligibility Criteria

Inclusion

  • Male and female subjects greater than or equal to 18 years,
  • Subjects currently on oral vitamin K antagonist (VKA) therapy,
  • An urgent surgical procedure is required within 24 hours of the start of investigational medicinal product (IMP),
  • Due to the nature of the procedure, withdrawal of oral VKA therapy and infusion of plasma are also indicated to reverse the VKA effect,
  • INR greater than or equal to 2 within 3 hours before start of IMP,
  • Informed consent has been obtained.

Exclusion

  • Subjects requiring urgent surgical procedures where according to the surgeon's clinical judgment, an accurate estimate of blood loss is not possible (e.g., ruptured aneurysm),
  • Subjects for whom administration of intravenous vitamin K and vitamin K antagonists withdrawal alone can adequately correct the subject's coagulopathy before initiation of the urgent surgical procedure,
  • Administration of intravenous vitamin K more than 3 hours or administration of oral vitamin K more than 6 hours prior to infusion of IMP,
  • Subjects in whom lowering INR within normal range may present an unacceptable risk for a thromboembolic complication where the INR goal is to lower but not normalize the INR because of risk of a procedure-associated stroke,
  • Subjects, who despite medical management that includes close monitoring and diuretics, may not, by investigator assessment, tolerate the total volume of IMP required by the protocol,
  • Expected need for additional non-study blood products before infusion of IMP (Note: Administration of packed red blood cells is not an exclusion criterion),
  • Expected need for platelet transfusions or desmopressin before Day 10,
  • Acute trauma for which reversal of vitamin K antagonists alone would not be expected to control or resolve an acute bleeding complication and/or control the acute bleeding event,
  • Unfractionated or low molecular weight heparin use within 24 hours before randomization or potential need before completion of the procedure,
  • History of thromboembolic event, myocardial infarction, unstable angina pectoris, critical aortic stenosis, cerebral vascular accident, transient ischemic attack, severe peripheral vascular disease, disseminated intravascular coagulation within 3 months of enrollment,
  • Reversal of VKA therapy alone may not resolve the coagulopathy (eg, receiving a potent anti-platelet agent, i.e., clopidogrel or prasugrel, or advanced liver disease),
  • Known history of antiphospholipid antibody syndrome or lupus anticoagulant antibodies,
  • Suspected or confirmed serious viral or bacterial infection, e.g., meningitis, or sepsis at time of enrollment,
  • Administration of whole blood, plasma, plasma fractions or platelets within 2 weeks prior to inclusion into the study (Note: Administration of packed red blood cells is not an exclusion criterion),
  • Pre-existing progressive fatal disease with a life expectancy of less than 2 months,
  • Known inhibitors to coagulation factors II, VII, IX, or X; or hereditary protein C or protein S deficiency; or heparin-induced, type II thrombocytopenia,
  • Treatment with any other investigational medicinal product within 30 days prior to inclusion into the study,
  • Presence or history of hypersensitivity to components of the study medication,
  • Pregnant or breast-feeding women,
  • Prior inclusion in this study or any other CSL Behring sponsored Beriplex study,
  • For subjects with intracranial hemorrhage with:
  • Glasgow Coma Score \<10 (see Appendix 8)
  • Modified Rankin Score \> 3 prior to ICH (see Appendix 9)
  • Intracerebral hemorrhage
  • Epidural hematomas
  • Infratentorial hemorrhage
  • Subarachnoid hemorrhage (SAH) subjects with a Hunt and Hess Scale \>2
  • Subdural hematomas that:
  • are judged to be an acute subdural hematoma (based on neurosurgeon review)
  • have a concurrent SAH or parenchymal contusion

Key Trial Info

Start Date :

February 1 2009

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

February 1 2013

Estimated Enrollment :

176 Patients enrolled

Trial Details

Trial ID

NCT00803101

Start Date

February 1 2009

End Date

February 1 2013

Last Update

April 6 2015

Active Locations (30)

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Page 1 of 8 (30 locations)

1

Study Site

Newark, Delaware, United States, 19718

2

Study site

Lexington, Kentucky, United States, 40536

3

Study Site

Boston, Massachusetts, United States, 02114

4

Study Site

Duluth, Minnesota, United States, 55805