Study of a Prothrombin Complex Concentrate for Rapid Reversal of Coagulopathy Induced by Vitamin K Antagonists in Japanese Subjects

CSL Behring11 enrolled

Overview

The purpose of this study is to evaluate efficacy and safety of a Prothrombin Complex Concentrate (PCC), BE1116. BE1116 will be used for the rapid reversal of coagulopathy induced by vitamin K antagonists in Japanese subjects who require immediate correction of international normalized ratio (INR) due to a major bleed or emergency surgery.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Major Bleeding Reversal of Coagulopathy

Interventions

BE1116 (Prothrombin Complex Concentrate)BIOLOGICAL

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male and female Japanese subjects greater than or equal to 20 years * Subjects currently on vitamin K antagonist (VKA) therapy * INR greater than or equal to 2 within 3 hours before start of BE1116 infusion * Urgent reversal of VKA therapy for a surgical or invasive medical procedure is required within 24 hours of the start of BE1116 infusion, or presentation with an acute major bleed Exclusion Criteria: * Subjects for whom administration of I.V. vitamin K and VKA withdrawal, alone, can adequately correct the subject's coagulopathy before the infusion of BE1116 * Subjects in whom lowering the INR to within the normal range is not a treatment goal * Use of anticoagulants other than VKAs (or expected use within 1 day) * Medical history for which PCCs are contraindicated * History of thromboembolic event within 3 months of screening * Congenital or acquired abnormality of hemostasis other than receipt of VKAs * Administration of whole blood, plasma, plasma fractions, or platelets within 2 weeks prior to the start of BE1116 infusion * For subjects with intracranial hemorrhage (ICH): * Glasgow Coma Score (GCS) \< 7 * Intracerebral hematoma volume \> 30 cm3 as assessed by computed tomography (CT) scan * For subdural hematomas: maximum thickness ≥ 10 mm, midline shift ≥ 5 mm, or acute subdural hematomas (based on neurosurgeon review) * For subarachnoid hemorrhage: any evidence of hydrocephalus, or Hunt and Hess Scale \> 2, or concomitant subdural hematoma * Infratentorial ICH location * Epidural hematomas * Intraventricular rupture of hemorrhage * Requires surgical intervention

Locations (11)

Nippon Medical School Hospital

Sendagi, Bunkyo, Japan

Kyushu Medical Center

Chūōku, Fukuoka, Japan

Nippon Medical School Chiba Hokusoh Hospital

Kamagari, Inzai, Japan

Outcomes

Primary Outcomes

Percentage of Subjects With a Rapid Reversal of VKA Effect

A rapid reversal of (Vitamin K antagonist) VKA effect is a reduction of the INR to ≤ 1.3 at 30 minutes after the end of infusion.

Time frame: At baseline and at 30 minutes after the end of infusion

Secondary Outcomes

Percentage of Subjects Achieving Hemostatic Efficacy During Surgery

Hemostatic efficacy is the binary endpoint of effective or non-effective hemostasis, where 'effective' is a hemostatic efficacy rating of "very good" or "satisfactory", and 'non-effective' is a hemostatic efficacy rating of "questionable" or "none".

Time frame: From the start of surgery/procedure until the end of surgery/procedure

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

Hemostatic efficacy is the binary endpoint of effective or non-effective hemostasis, where 'effective' is a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' is a hemostatic efficacy rating of "poor/none".

Time frame: Baseline CT scan, baseline haematology or the end of infusion, until 24 hours after the end of infusion

Increase in Plasma Levels of Factor (F)II, FVII, FIX, and FX, and Protein C and Protein S

The increase in plasma levels is assessed through response and in vivo recovery (IVR) of FII, FVII, FIX, FX, and protein C and protein S. The incremental IVR \[(IU/dL)/(IU/kg)\] is calculated as follows: (IU/dL activity rise in plasma)/(IU/kg body weight infused) = \[maximum increase in component plasma level within 3 hours compared to pre-infusion (IU/dL)\]/{\[exact dose of component in drug administered (IU)\]/\[body weight (kg)\]}.

Time frame: Before infusion and up to 3 h after the start of infusion

Percentage of Subjects With INR Correction

The time taken from the start of infusion to INR correction (defined as an INR ≤ 1.3) is recorded. The percentage of participants with INR correction is calculated.

Data from ClinicalTrials.gov

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