Clinical trial NCT00708435: Efficacy and Safety Study of BERIPLEX® P/N (Kcentra) Compared With Plasma in Patients With Acute Major Bleeding Caused by Anticoagulant Therapy
Official title: An Open-label, Randomized, Multicenter Phase IIIb Study to Assess the Efficacy, Safety and Tolerance of BERIPLEX® P/N Compared With Plasma for Rapid Reversal of Coagulopathy Induced by Coumarin Derivatives in Subjects With Acute Major Bleeding
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Blood Coagulation Disorders
Acute Major Bleeding
Keywords: Anticoagulant reversal
Prothrombin
Complex
Concentrate
Coagulopathy
induced by
coumarin
derivatives
Kcentra
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2008-07-02
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate efficacy, safety and tolerance of BERIPLEX® P/N (Kcentra) compared with plasma in regard to rapid reversal of coagulopathy induced by coumarin derivatives in subjects who require immediate correction of INR (International Normalized Ratio)and to stop an acute major bleeding.


Eligibility criteria: Inclusion Criteria:

* Male and female subjects ≥ 18 years
* Subjects who have received oral vitamin K-antagonist therapy
* Subjects who have acute major bleeding, defined as one of the following: life-threatening or potentially life-threatening, acute bleeding associated with a fall in hemoglobin (Hb) level ≥ 2g/dL, bleeding requiring blood product transfusion
* INR ≥ 2 within 3 hours before start of study treatment
* Informed consent has been obtained

Exclusion Criteria:

* Expected survival of less than 3 days, or expected surgery in less than 1 day
* Acute trauma for which reversal of vitamin K antagonists alone would not be expected to control the acute bleeding event
* Use of unfractionated or low molecular weight heparin use from 24 hours prior to enrollment or expected need within 24 hours after start of infusion
* For patients with ICH: Glasgow coma score (GCS) \< 7; intracerebral hematoma volume \> 30cc as assessed by ABC/21; for subdural hematomas: maximum thickness ≥ 10 mm, midline shift ≥ 5 mm; for subarachnoid hemorrhage: any evidence of hydrocephalus; infratentorial ICH location; epidural hematomas; intraventricular extension of hemorrhage; modified Rankin score (mRS) of \>3 prior to ICH
* History of thrombotic event, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within 3 months of enrollment
* Known history of antiphospholipid antibody syndrome or lupus anticoagulant antibodies
* Suspected or confirmed sepsis at time of enrollment
* Administration of whole blood, plasma, plasma fractions or platelets within 2 weeks prior to inclusion into the study
* Large blood vessel rupture (e.g. in advanced cancer patient)
* Pre-existing progressive fatal disease with a life expectancy of less than 2 months
* Known inhibitors to coagulation factors II, VII, IX, or X; or hereditary protein C or protein S deficiency; or heparin-induced, type II thrombocytopenia
* Treatment with any other investigational medicinal product within 30 days prior to inclusion into the study
* Presence or history of hypersensitivity to components of the study medication
* Pregnant or breast-feeding women
* Prior inclusion in this study or any other CSL Behring-sponsored Beriplex study

Primary outcomes:
measure: Percentage of Participants Achieving Hemostatic Efficacy of Stopping an Ongoing Major Bleed
timeFrame: At 1 and 4 hours after the end of infusion
measure: Percentage of Participants Who Had a Rapid Decrease of the International Normalized Ratio (INR)
timeFrame: 30 minutes after end of infusion
Secondary outcomes:
measure: Percentage of Participants Who Had Hemostatic Efficacy for Visible or Non-visible Musculoskeletal Bleeding
timeFrame: At 3 and 6 hours after the start of infusion
measure: Incremental in Vivo Recovery (IVR) (Response) of Factors II, VII, IX, and X, Protein C, and Protein S for Beriplex
timeFrame: Before infusion and up to 3 h after the start of infusion
measure: Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S
timeFrame: From preinfusion until 24 h after the start of infusion
measure: Percentage of Participants With INR Correction at Various Times After the Start of Infusion
timeFrame: From the start of infusion until INR correction; calculated at 0.5, 1, 3, 6, 12, and 24 h after the start of infusion.
measure: Percentage of Participants With INR Correction at Various Times After Randomization
timeFrame: From randomization until INR correction; calculated at 2.5, 3, 5, 8, 14, and 26 h after randomization.
measure: Transfusion of Red Blood Cells
timeFrame: From the start of infusion until 24 h after the start of infusion
measure: Use of 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 10 visit for non-serious AEs and from the start of infusion up to the allowed time window of the Day 45 visit for SAEs.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Study Site
state: Alabama
city: Los Angeles
country: United States
facility: Study Site
state: California
city: San Franciso
country: United States
facility: Study Site
state: California
city: Newark
country: United States
facility: Study Site
state: Delaware
city: Orlando
country: United States
facility: Study Site
state: Florida
city: Tampa
country: United States
facility: Study Site
state: Florida
city: Chicago
country: United States
facility: Study Site
state: Illinois
city: Oak Park
country: United States
facility: Study Site
state: Illinois
city: Hazard
country: United States
facility: Study Site
state: Kentucky
city: Baltimore
country: United States
facility: Study Site
state: Maryland
city: Baltimore
country: United States
facility: Study Site
state: Maryland
city: Boston
country: United States
facility: Study Site
state: Massachusetts
city: Worchester
country: United States
facility: Study Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Study Site
state: Michigan
city: Royal Oak
country: United States
facility: Study Site
state: Michigan
city: Duluth
country: United States
facility: Study Site
state: Minnesota
city: Minneapolis
country: United States
facility: Study Site
state: Minnesota
city: Jackson
country: United States
facility: Study Site
state: Mississippi
city: St. Louis
country: United States
facility: Study Site
state: Missouri
city: Albuquerque
country: United States
facility: Study Site
state: New Mexico
city: Albany
country: United States
facility: Study Site
state: New York
city: Johnson City
country: United States
facility: Study Site
state: New York
city: New York
country: United States
facility: Study Site
state: New York
city: New York
country: United States
facility: Study Site
state: New York
city: New York
country: United States
facility: Study Site
state: New York
city: Rochester
country: United States
facility: Study Site
state: New York
city: Staten Island
country: United States
facility: Study Site
state: New York
city: Durham
country: United States
facility: Study Site
state: North Carolina
city: Allentown
country: United States
facility: Study Site
state: Pennsylvania
city: Hershey
country: United States
facility: Study Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Study Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Study Site
state: Pennsylvania
city: West Reading
country: United States
facility: Study Site
state: Pennsylvania
city: Austin
country: United States
facility: Study Site
state: Texas
city: El Paso
country: United States
facility: Study Site
state: Texas
city: Houston
country: United States
facility: Study Site 2
state: Texas
city: Houston
country: United States
facility: Study Site
state: Texas
city: Temple
country: United States
facility: Study Site
state: Texas
city: Salt Lake City
country: United States
facility: Study Site
state: Utah
city: Charlottesville
country: United States
facility: Study Site
state: Virginia
city: Richmond
country: United States
facility: Study Site
state: Virginia
city: Minsk
country: Belarus
facility: Study Site 1
city: Minsk
country: Belarus
facility: Study Site 2
city: Pleven
country: Bulgaria
facility: Study Site
city: Plovdiv
country: Bulgaria
facility: Study Site
city: Rousse
country: Bulgaria
facility: Study Site
city: Sofia
country: Bulgaria
facility: Study Site 1
city: Sofia
country: Bulgaria
facility: Study Site 2
city: Sofia
country: Bulgaria
facility: Study Site 3
city: Sofia
country: Bulgaria
facility: Study Site 4
city: Brasov
country: Romania
facility: Study Site
city: Bucharest
country: Romania
facility: Study Site 1
city: Bucharest
country: Romania
facility: Study Site 2
city: Bucharest
country: Romania
facility: Study Site 3
city: Cluj-Napoca
country: Romania
facility: Study Site
city: Timisoara
country: Romania
facility: Study Site
city: Arkhangelsk
country: Russian Federation
facility: Study Site
city: Barnaul
country: Russian Federation
facility: Study Site 1
city: Barnaul
country: Russian Federation
facility: Study Site 2
city: Kazan
country: Russian Federation
facility: Study Site
city: Kemerovo
country: Russian Federation
facility: Study Site
city: Moscow
country: Russian Federation
facility: Study Site 1
city: Moscow
country: Russian Federation
facility: Study Site 2
city: Nizhny Novgorod
country: Russian Federation
facility: Study Site 1
city: Nizhny Novgorod
country: Russian Federation
facility: Study Site 2
city: St. Petersburg
country: Russian Federation
facility: Study Site 1
city: St. Petersburg
country: Russian Federation
facility: Study Site 2
city: Kharkov
country: Ukraine
facility: Study Site
city: Vinnytsa
country: Ukraine
facility: Study Site
Study officials:
affiliation: CSL Behring
name: Program Director, Clinical R&D
role: STUDY_DIRECTOR
References:
citation: Sarode R, Milling TJ Jr, Refaai MA, Mangione A, Schneider A, Durn BL, Goldstein JN. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013 Sep 10;128(11):1234-43. doi: 10.1161/CIRCULATIONAHA.113.002283. Epub 2013 Aug 9.