Efficacy and Safety Study of BERIPLEX® P/N (Kcentra) Compared With Plasma in Patients With Acute Major Bleeding Caused by Anticoagulant Therapy

CSL Behring216 enrolled

Overview

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 coumarin derivatives in subjects who require immediate correction of INR (International Normalized Ratio)and to stop an acute major bleeding.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

216

Conditions

Blood Coagulation Disorders Acute Major Bleeding

Interventions

Beriplex® P/N (Kcentra)BIOLOGICAL

Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight

Fresh frozen plasmaBIOLOGICAL

Intravenous Infusion, dosage depending on baseline INR and body weight

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male and female subjects ≥ 18 years * Subjects who have received oral vitamin K-antagonist therapy * Subjects who have acute major bleeding, defined as one of the following: life-threatening or potentially life-threatening, acute bleeding associated with a fall in hemoglobin (Hb) level ≥ 2g/dL, bleeding requiring blood product transfusion * INR ≥ 2 within 3 hours before start of study treatment * Informed consent has been obtained Exclusion Criteria: * Expected survival of less than 3 days, or expected surgery in less than 1 day * Acute trauma for which reversal of vitamin K antagonists alone would not be expected to control the acute bleeding event * Use of unfractionated or low molecular weight heparin use from 24 hours prior to enrollment or expected need within 24 hours after start of infusion * For patients with ICH: Glasgow coma score (GCS) \< 7; intracerebral hematoma volume \> 30cc as assessed by ABC/21; for subdural hematomas: maximum thickness ≥ 10 mm, midline shift ≥ 5 mm; for subarachnoid hemorrhage: any evidence of hydrocephalus; infratentorial ICH location; epidural hematomas; intraventricular extension of hemorrhage; modified Rankin score (mRS) of \>3 prior to ICH * History of thrombotic event, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within 3 months of enrollment * Known history of antiphospholipid antibody syndrome or lupus anticoagulant antibodies * Suspected or confirmed sepsis at time of enrollment * Administration of whole blood, plasma, plasma fractions or platelets within 2 weeks prior to inclusion into the study * Large blood vessel rupture (e.g. in advanced cancer patient) * 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

Locations (69)

Outcomes

Primary Outcomes

Percentage of Participants Achieving Hemostatic Efficacy of Stopping an Ongoing Major Bleed

Hemostatic efficacy was determined by a blinded independent board as excellent, good, or poor/none, based on prespecified definitions. Assessments of visible or non-visible musculoskeletal bleeding were made at 1 and 4 hours after the end of infusion. Hemostatic efficacy was the binary endpoint of effective or non-effective hemostasis, where 'effective' was a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' was a hemostatic efficacy rating of "poor/none".

Time frame: At 1 and 4 hours after the end of infusion

Percentage of Participants Who Had a Rapid Decrease of the International Normalized Ratio (INR)

A rapid decrease of the international normalized ratio (INR) was defined as an INR ≤ 1.3 at 30 minutes after the end of the infusion. The INR is a standard way to describe the time it takes for blood to clot; an INR range of 0.8 to 1.2 is considered normal for a healthy person who is not using oral anticoagulant therapy.

Time frame: 30 minutes after end of infusion

Secondary Outcomes

Percentage of Participants Who Had Hemostatic Efficacy for Visible or Non-visible Musculoskeletal Bleeding

Hemostatic efficacy was determined by a blinded independent board as excellent, good, or poor/none, based on prespecified definitions. Assessments of visible or non-visible musculoskeletal bleeding were made at 3 and 6 hours after the start of infusion. Hemostatic efficacy was the binary endpoint of effective or non-effective hemostasis, where 'effective' was a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' was a hemostatic efficacy rating of "poor/none".

Time frame: At 3 and 6 hours after the start of infusion

Incremental in Vivo Recovery (IVR) (Response) of Factors II, VII, IX, and X, Protein C, and Protein S for Beriplex

The incremental IVR \[(IU/dL)/(IU/kg)\] was calculated as follows: (IU/dL activity rise in plasma)/(IU/kg body weight infused) = \[maximum increase in component plasma level within 3 hours compared to pre-infusion (IU/dL)\]/{\[exact dose of component in drug administered (IU)\]/\[body weight (kg)\]}.

Data from ClinicalTrials.gov

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Study Site

Birmingham, Alabama, United States

Study Site

Los Angeles, California, United States

Study Site

San Franciso, California, United States

Study Site

Newark, Delaware, United States

Study Site

Orlando, Florida, United States

Study Site

Tampa, Florida, United States

Study Site

Chicago, Illinois, United States

Study Site

Oak Park, Illinois, United States

Study Site

Hazard, Kentucky, United States

Study Site

Baltimore, Maryland, United States

...and 59 more locations