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

NCT02281201 | Completed Phase 3

• 1 other identifier: BE1116_3004
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 11

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.

Conditions

Acute Major Bleeding; Reversal of Coagulopathy

Outcome Measures

Primary Outcomes (1)

• 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.

  At baseline and at 30 minutes after the end of infusion

Secondary Outcomes (15)

• Percentage of Subjects Achieving Hemostatic Efficacy During Surgery

  From the start of surgery/procedure until the end of surgery/procedure

• 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

• 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

• Percentage of Subjects With INR Correction

  From the start of infusion until INR correction, up to 24 hours after the end of infusion

• 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

Study Arms (1)

BE1116

EXPERIMENTAL

Single intravenous (I.V.) infusion, dosage depending on baseline INR and body weight

Biological: BE1116 (Prothrombin Complex Concentrate)

Interventions

BE1116 (Prothrombin Complex Concentrate) BIOLOGICAL

Also known as: Beriplex® P/N, KcentraTM, Confidex®

BE1116

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (11)

Nippon Medical School Hospital

Sendagi, Bunkyo, 113-8603, Japan

Location

Kyushu Medical Center

Chūōku, Fukuoka, 810-8563, Japan

Location

Nippon Medical School Chiba Hokusoh Hospital

Kamagari, Inzai, 270-1694, Japan

Location

Kurashiki Central Hospital

Miwa, Kurashiki, 710-0052, Japan

Location

Osaka National Hospital

Chuo-ku, Osaka, 540-0006, Japan

Location

Kinki University

Higashiosaka, Osaka, 577-0818, Japan

Location

National Cerebral and Cardiovascular Center

Suita, Osaka, 565-0873, Japan

Location

Tohoku University Hospital

Aoba-ku, Sendai, 980-8574, Japan

Location

National Center for Global Health and Medicine

Toyama, Shinjuku, 162-0052, Japan

Location

Osaka University Hospital

Yamadaoka, Suita, 565-0871, Japan

Location

St. Luke's International Hospital

Chūō, Tokyo, 104-8560, Japan

Location

MeSH Terms

Interventions

Factor IX

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Study Officials

• Program Director, Acquired Bleeding

  CSL Behring

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2014
• First Posted: November 3, 2014
• Study Start: October 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: March 1, 2016
• Last Updated: May 4, 2016

Record last verified: 2016-04

Locations

JP (11)