Trial record 2 of 8 for:    beriplex p/n

Efficacy and Safety Study of BERIPLEX® P/N (Kcentra) Compared With Plasma in Patients With Acute Major Bleeding Caused by Anticoagulant Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT00708435
First received: July 1, 2008
Last updated: January 1, 2014
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Blood Coagulation Disorders
Acute Major Bleeding
Biological: Beriplex® P/N (Kcentra)
Biological: Fresh frozen plasma
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • Percentage of Participants Achieving Hemostatic Efficacy of Stopping an Ongoing Major Bleed [ Time Frame: At 1 and 4 hours after the end of infusion ] [ Designated as safety issue: No ]
    Hemostatic efficacy was determined by a blinded independent board as excellent, good, or poor/none, based on prespecified definitions. Assessments of visible or non-visible musculoskeletal bleeding were made at 1 and 4 hours after the end of infusion. Hemostatic efficacy was the binary endpoint of effective or non-effective hemostasis, where 'effective' was a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' was a hemostatic efficacy rating of "poor/none".

  • Percentage of Participants Who Had a Rapid Decrease of the International Normalized Ratio (INR) [ Time Frame: 30 minutes after end of infusion ] [ Designated as safety issue: No ]
    A rapid decrease of the international normalized ratio (INR) was defined as an INR ≤ 1.3 at 30 minutes after the end of the infusion. The INR is a standard way to describe the time it takes for blood to clot; an INR range of 0.8 to 1.2 is considered normal for a healthy person who is not using oral anticoagulant therapy.


Secondary Outcome Measures:
  • Percentage of Participants Who Had Hemostatic Efficacy for Visible or Non-visible Musculoskeletal Bleeding [ Time Frame: At 3 and 6 hours after the start of infusion ] [ Designated as safety issue: No ]
    Hemostatic efficacy was determined by a blinded independent board as excellent, good, or poor/none, based on prespecified definitions. Assessments of visible or non-visible musculoskeletal bleeding were made at 3 and 6 hours after the start of infusion. Hemostatic efficacy was the binary endpoint of effective or non-effective hemostasis, where 'effective' was a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' was a hemostatic efficacy rating of "poor/none".

  • Incremental in Vivo Recovery (IVR) (Response) of Factors II, VII, IX, and X, Protein C, and Protein S for Beriplex [ Time Frame: Before infusion and up to 3 h after the start of infusion ] [ Designated as safety issue: No ]
    The incremental IVR [(IU/dL)/(IU/kg)] was 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)]}.

  • Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S [ Time Frame: From preinfusion until 24 h after the start of infusion ] [ Designated as safety issue: No ]
    Plasma levels are presented as the percentage of normal at pre-infusion and 30 min and 24 h after the start of infusion. The plasma level assay results are reported as a potency relative to a standard, where 100% is considered to be normal.

  • Percentage of Participants With INR Correction at Various Times After the Start of Infusion [ Time Frame: From the start of infusion until INR correction; calculated at 0.5, 1, 3, 6, 12, and 24 h after the start of infusion. ] [ Designated as safety issue: No ]
    The time taken from the start of infusion to INR correction (defined as an INR ≤ 1.3) was recorded. The percentage of participants with INR correction was calculated at 0.5, 1, 3, 6, 12, and 24 h after the start of infusion.

  • Percentage of Participants With INR Correction at Various Times After Randomization [ Time Frame: From randomization until INR correction; calculated at 2.5, 3, 5, 8, 14, and 26 h after randomization. ] [ Designated as safety issue: No ]
    The time taken from randomization to INR correction (defined as an INR ≤ 1.3) was recorded. The percentage of participants with INR correction was calculated at 2.5, 3, 5, 8, 14, and 26 h after randomization.

  • Transfusion of Red Blood Cells [ Time Frame: From the start of infusion until 24 h after the start of infusion ] [ Designated as safety issue: No ]
    Red blood cells were packed red blood cells (PRBCs).

  • Use of Other Blood Products and Hemostatic Agents [ Time Frame: From the start of infusion until 24 h after the start of infusion ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Overall Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
    Number of participants with TEAEs. Treatment-related AEs were defined as events whose relationship to study treatment was definitely related, probably related, or possibly related in the opinion of the investigator. AEs with missing relationship were considered related to treatment. Serious TEAEs were treatment-emergent SAEs. Deaths reported up to and including Day 45; one additional Beriplex death occurred after Day 45.


Enrollment: 216
Study Start Date: June 2008
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Beriplex® P/N Biological: Beriplex® P/N (Kcentra)
Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight
Other Name: Kcentra
Active Comparator: Fresh frozen plasma Biological: Fresh frozen plasma
Intravenous Infusion, dosage depending on baseline INR and body weight

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00708435

  Show 69 Study Locations
Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Program Director, Clinical R&D CSL Behring
  More Information

Additional Information:
Publications:
Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT00708435     History of Changes
Other Study ID Numbers: BE1116_3002, 1462, 2007-007861-19
Study First Received: July 1, 2008
Results First Received: June 7, 2013
Last Updated: January 1, 2014
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
Ukraine: State Pharmacological Center - Ministry of Health
Armenia: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Belarus: Ministry of Health
Romania: National Medicines Agency

Keywords provided by CSL Behring:
Anticoagulant reversal
Prothrombin
Complex
Concentrate
Coagulopathy
induced by
coumarin
derivatives
Kcentra

Additional relevant MeSH terms:
Blood Coagulation Disorders
Hemostatic Disorders
Hemorrhage
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Pathologic Processes
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014