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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02281201
First Posted: November 3, 2014
Last Update Posted: May 4, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
CSL Behring
  Purpose
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.

Condition Intervention Phase
Acute Major Bleeding Reversal of Coagulopathy Biological: BE1116 (Prothrombin Complex Concentrate) Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Uncontrolled, Single-arm, Multicenter Phase IIIb Study to Assess the Efficacy and Safety of BE1116 in Japanese Subjects Receiving Vitamin K Antagonist Therapy With an Elevated INR and Either Acute Major Bleeding or a Requirement for Urgent Reversal of Vitamin K Antagonist Therapy for a Surgical or Invasive Medical Procedure

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • Percentage of Subjects With a Rapid Reversal of VKA Effect [ Time Frame: 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:
  • Percentage of Subjects Achieving Hemostatic Efficacy During Surgery [ Time Frame: 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 [ Time Frame: 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".

  • Increase in Plasma Levels of Factor (F)II, FVII, FIX, and FX, and Protein C and Protein S [ Time Frame: 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 With INR Correction [ Time Frame: 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 [ Time Frame: 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.

  • Percentage of Subjects Who Receive Red Blood Cells [ Time Frame: From the start of infusion until 24 h after the start of infusion ]
    Red blood cells are packed red blood cells (PRBCs).

  • Percentage of Subjects Who Receive Other Blood Products and Hemostatic Agents [ Time Frame: 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.

  • 45-Day All-cause Mortality [ Time Frame: Until Day 45 ]
  • Overall Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 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 modified Rankin Scale for all subjects with intracranial haemorrhage [ Time Frame: Before infusion and at Day 45 ]
  • Mean Predicted and Actual Blood Loss (mls) for all Surgical/Invasive Procedures [ Time Frame: From the start of surgery/procedure until the end of surgery/procedure ]
  • Mean Volume (mls) of Wound Drainage for all Surgical/Invasive Procedures [ Time Frame: From the start of wound drainage until the end of wound drainage, up to the final safety follow-up visit (Day 45) ]
  • Mean Time (mins) Between Last Suture and Cessation of Wound Drainage for all Surgical/Invasive Procedure [ Time Frame: From the time of last suture until the end of wound drainage, up to the final safety follow-up visit (Day 45) ]
  • Vital signs [ Time Frame: 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)

  • Viral serology [ Time Frame: 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.


Enrollment: 11
Study Start Date: October 2014
Study Completion Date: March 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BE1116
Single intravenous (I.V.) infusion, dosage depending on baseline INR and body weight
Biological: BE1116 (Prothrombin Complex Concentrate)
Other Names:
  • Beriplex® P/N
  • KcentraTM
  • Confidex®

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02281201


Locations
Japan
Nippon Medical School Hospital
Sendagi, Bunkyo, Japan, 113-8603
Kyushu Medical Center
Chuo-ku, Fukuoka, Japan, 810-8563
Nippon Medical School Chiba Hokusoh Hospital
Kamagari, Inzai, Japan, 270-1694
Kurashiki Central Hospital
Miwa, Kurashiki, Japan, 710-0052
Osaka National Hospital
Chuo-ku, Osaka, Japan, 540-0006
Kinki University
Higashiosaka, Osaka, Japan, 577-0818
National Cerebral and Cardiovascular Center
Suita, Osaka, Japan, 565-0873
Tohoku University Hospital
Aoba-ku, Sendai, Japan, 980-8574
National Center for Global Health and Medicine
Toyama, Shinjuku, Japan, 162-0052
Osaka University Hospital
Yamadaoka, Suita, Japan, 565-0871
St. Luke's International Hospital
Chuo, Tokyo, Japan, 104-8560
Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Program Director, Acquired Bleeding CSL Behring
  More Information

Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT02281201     History of Changes
Other Study ID Numbers: BE1116_3004
First Submitted: October 27, 2014
First Posted: November 3, 2014
Last Update Posted: May 4, 2016
Last Verified: April 2016

Additional relevant MeSH terms:
Hemorrhage
Blood Coagulation Disorders
Hemostatic Disorders
Pathologic Processes
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Vitamins
Vitamin K
Thrombin
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants