Clinical trial NCT02281201: Study of a Prothrombin Complex Concentrate for Rapid Reversal of Coagulopathy Induced by Vitamin K Antagonists in Japanese Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Major Bleeding
Reversal of Coagulopathy
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2014-11-02
Enrollment: 11
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of Subjects With a Rapid Reversal of VKA Effect
timeFrame: At baseline and at 30 minutes after the end of infusion
Secondary outcomes:
measure: Percentage of Subjects Achieving Hemostatic Efficacy During Surgery
timeFrame: From the start of surgery/procedure until the end of surgery/procedure
measure: Percentage of Subjects Achieving Hemostatic Efficacy of Stopping an Ongoing Major Bleed
timeFrame: Baseline CT scan, baseline haematology or the end of infusion, until 24 hours after the end of infusion
measure: Increase in Plasma Levels of Factor (F)II, FVII, FIX, and FX, and Protein C and Protein S
timeFrame: Before infusion and up to 3 h after the start of infusion
measure: Percentage of Subjects With INR Correction
timeFrame: From the start of infusion until INR correction, up to 24 hours after the end of infusion
measure: Percentage of Subjects With INR Correction at Various Times After the End of Infusion
timeFrame: From the end of infusion until INR correction; calculated at 0.5, 1, 3, 6, 12, and 24 h after the end of infusion
measure: Percentage of Subjects Who Receive Red Blood Cells
timeFrame: From the start of infusion until 24 h after the start of infusion
measure: Percentage of Subjects Who Receive Other Blood Products and Hemostatic Agents
timeFrame: From the start of infusion until 24 h after the start of infusion
measure: 45-Day All-cause Mortality
timeFrame: Until Day 45
measure: Overall Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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
measure: Mean modified Rankin Scale for all subjects with intracranial haemorrhage
timeFrame: Before infusion and at Day 45
measure: Mean Predicted and Actual Blood Loss (mls) for all Surgical/Invasive Procedures
timeFrame: From the start of surgery/procedure until the end of surgery/procedure
measure: Mean Volume (mls) of Wound Drainage for all Surgical/Invasive Procedures
timeFrame: From the start of wound drainage until the end of wound drainage, up to the final safety follow-up visit (Day 45)
measure: Mean Time (mins) Between Last Suture and Cessation of Wound Drainage for all Surgical/Invasive Procedure
timeFrame: From the time of last suture until the end of wound drainage, up to the final safety follow-up visit (Day 45)
measure: Vital signs
timeFrame: At baseline and until 24 hours after the end of infusion
measure: Viral serology
timeFrame: At baseline and until Day 45
Other outcomes:
Locations:
city: Sendagi
country: Japan
facility: Nippon Medical School Hospital
state: Bunkyo
city: Chuo-ku
country: Japan
facility: Kyushu Medical Center
state: Fukuoka
city: Kamagari
country: Japan
facility: Nippon Medical School Chiba Hokusoh Hospital
state: Inzai
city: Miwa
country: Japan
facility: Kurashiki Central Hospital
state: Kurashiki
city: Chuo-ku
country: Japan
facility: Osaka National Hospital
state: Osaka
city: Higashiosaka
country: Japan
facility: Kinki University
state: Osaka
city: Suita
country: Japan
facility: National Cerebral and Cardiovascular Center
state: Osaka
city: Aoba-ku
country: Japan
facility: Tohoku University Hospital
state: Sendai
city: Toyama
country: Japan
facility: National Center for Global Health and Medicine
state: Shinjuku
city: Yamadaoka
country: Japan
facility: Osaka University Hospital
state: Suita
city: Chuo
country: Japan
facility: St. Luke's International Hospital
state: Tokyo
Study officials:
affiliation: CSL Behring
name: Program Director, Acquired Bleeding
role: STUDY_DIRECTOR
References: