Study of a Prothrombin Complex Concentrate for Rapid Reversal of Coagulopathy Induced by Vitamin K Antagonists in Japanese Subjects
- Conditions
- Acute Major BleedingReversal of Coagulopathy
- Interventions
- Biological: BE1116 (Prothrombin Complex Concentrate)
- Registration Number
- NCT02281201
- Lead Sponsor
- CSL Behring
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 11
- 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
-
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
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Administration of whole blood, plasma, plasma fractions, or platelets within 2 weeks prior to the start of BE1116 infusion
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BE1116 BE1116 (Prothrombin Complex Concentrate) Single intravenous (I.V.) infusion, dosage depending on baseline INR and body weight
- Primary Outcome Measures
Name Time Method Percentage of Subjects With a Rapid Reversal of VKA Effect At baseline and at 30 minutes after the end of infusion 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.
- Secondary Outcome Measures
Name Time Method 45-Day All-cause Mortality Until Day 45 Overall Treatment-emergent Adverse Events (TEAEs) From the start of infusion up to the allowed time window of the Day 14 visit for non-serious AEs and from the start of infusion up to the allowed time window of the Day 45 visit for SAEs Number of participants with TEAEs. TEAEs are defined as adverse events that developed or worsened following exposure to investigational medicinal product. Serious TEAEs are treatment-emergent serious adverse events (SAEs).
Mean Predicted and Actual Blood Loss (mls) for all Surgical/Invasive Procedures From the start of surgery/procedure until the end of surgery/procedure Mean Time (mins) Between Last Suture and Cessation of Wound Drainage for all Surgical/Invasive Procedure From the time of last suture until the end of wound drainage, up to the final safety follow-up visit (Day 45) Viral serology At baseline and until Day 45 Percentage of participants with negative viral serology (for Human immunodeficiency virus, Hepatitis B, Hepatitis A, Hepatitis C and Parvovirus B19) before infusion who become positive after infusion.
Mean modified Rankin Scale for all subjects with intracranial haemorrhage Before infusion and at Day 45 Increase in Plasma Levels of Factor (F)II, FVII, FIX, and FX, and Protein C and Protein S Before infusion and up to 3 h after the start of infusion 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) = \[maximum increase in component plasma level within 3 hours compared to pre-infusion (IU/dL)\]/{\[exact dose of component in drug administered (IU)\]/\[body weight (kg)\]}.
Percentage of Subjects Who Receive Red Blood Cells From the start of infusion until 24 h after the start of infusion Red blood cells are packed red blood cells (PRBCs).
Vital signs At baseline and until 24 hours after the end of infusion Percentage of participants with a clinically significant change in vital signs (including blood pressure, respiratory rate, temperature and pulse rate)
Percentage of Subjects Who Receive Other Blood Products and Hemostatic Agents From the start of infusion until 24 h after the start of infusion Other blood products and hemostatic agents containing coagulation factors (such as whole blood, plasma, albumin, platelets) not including PRBCs.
Percentage of Subjects Achieving Hemostatic Efficacy During Surgery From the start of surgery/procedure until the end of surgery/procedure 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".
Percentage of Subjects Achieving Hemostatic Efficacy of Stopping an Ongoing Major Bleed Baseline CT scan, baseline haematology or the end of infusion, until 24 hours after the end of infusion 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".
Percentage of Subjects With INR Correction From the start of infusion until INR correction, up to 24 hours after the end of infusion 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.
Percentage of Subjects With INR Correction at Various Times After the End of Infusion From the end of infusion until INR correction; calculated at 0.5, 1, 3, 6, 12, and 24 h after the end of infusion The time taken from the end of infusion to INR correction (defined as an INR ≤ 1.3) is recorded. The percentage of participants with INR correction at 0.5, 1, 3, 6, 12, and 24 h after the end of infusion is calculated.
Mean Volume (mls) of Wound Drainage for all Surgical/Invasive Procedures From the start of wound drainage until the end of wound drainage, up to the final safety follow-up visit (Day 45)
Trial Locations
- Locations (11)
Nippon Medical School Hospital
🇯🇵Sendagi, Bunkyo, Japan
Tohoku University Hospital
🇯🇵Aoba-ku, Sendai, Japan
Kurashiki Central Hospital
🇯🇵Miwa, Kurashiki, Japan
Kinki University
🇯🇵Higashiosaka, Osaka, Japan
National Cerebral and Cardiovascular Center
🇯🇵Suita, Osaka, Japan
Nippon Medical School Chiba Hokusoh Hospital
🇯🇵Kamagari, Inzai, Japan
Kyushu Medical Center
🇯🇵Chuo-ku, Fukuoka, Japan
Osaka National Hospital
🇯🇵Chuo-ku, Osaka, Japan
Osaka University Hospital
🇯🇵Yamadaoka, Suita, Japan
National Center for Global Health and Medicine
🇯🇵Toyama, Shinjuku, Japan
St. Luke's International Hospital
🇯🇵Chuo, Tokyo, Japan