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 (BE1116_3003)

CSL Behring

Status and phase: Completed; Phase 3

Conditions: Reversal of Coagulopathy

Treatments: Biological: Fresh frozen plasma; Biological: Beriplex® P/N (Kcentra)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00803101

2007-007862-39 (EudraCT Number)

BE1116_3003

1474 (Other Identifier)

Details and patient eligibility

About

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 subjects who require immediate correction of international normalized ratio (INR) because of emergency surgery.

Enrollment: 176 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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 criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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176 participants in 2 patient groups

Beriplex® P/N

Experimental group

Treatment:

Biological: Beriplex® P/N (Kcentra)

Fresh frozen plasma

Active Comparator group

Treatment:

Biological: Fresh frozen plasma