NCT00803101

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 vitamin K antagonists in subjects who require immediate correction of international normalized ratio (INR) because of emergency surgery.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
176

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Feb 2009

Typical duration for phase_3

Geographic Reach
6 countries

30 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 4, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 5, 2008

Completed
2 months until next milestone

Study Start

First participant enrolled

February 1, 2009

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2012

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2013

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

February 25, 2014

Completed
Last Updated

April 6, 2015

Status Verified

March 1, 2014

Enrollment Period

3.8 years

First QC Date

December 4, 2008

Results QC Date

January 12, 2014

Last Update Submit

March 18, 2015

Conditions

Reversal of Coagulopathy

Keywords

Anticoagulant reversalProthrombin Complex ConcentrateCoagulopathyCoumarin derivativesEmergency surgeryInvasive proceduresVitamin KReversal of coagulopathy induced by coumarin derivativesKcentra

Outcome Measures

Primary Outcomes (2)

  • Percentage of Participants Achieving Hemostatic Efficacy During Surgery

    Hemostatic efficacy was rated as excellent, good, or poor/none, based on prespecified definitions. 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".

    From the start of infusion until the end of surgery

  • Percentage of Participants Who Had a Rapid Decrease of the INR

    A rapid decrease of the INR was defined as an INR ≤ 1.3 at 30 minutes after the end of 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.

    30 minutes after the end of infusion

Secondary Outcomes (5)

  • Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S

    From pre-infusion until 24 h after the start of infusion

  • Transfusion of Packed Red Blood Cells (PRBCs) or Whole Blood

    From the start of surgery until 24 h after the start of surgery

  • Percentage of Participants With INR Correction at Various Times After the Start of Infusion

    From the start of infusion until INR correction; calculated at 0.5, 1, 3, 6, 12, and 24 h after the start of infusion

  • Percentage of Participants Who Received Red Blood Cells

    From the start of surgery until 24 h after the start of surgery

  • Overall Treatment-emergent Adverse Events (TEAEs)

    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

Study Arms (2)

Beriplex® P/N

EXPERIMENTAL
Biological: Beriplex® P/N (Kcentra)

Fresh frozen plasma

ACTIVE COMPARATOR
Biological: Fresh frozen plasma

Interventions

Beriplex® P/N (Kcentra)BIOLOGICAL

Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body-weight.

Also known as: Kcentra
Beriplex® P/N
Fresh frozen plasmaBIOLOGICAL

Intravenous infusion, dosage depending on baseline INR and body weight

Fresh frozen plasma

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male and female subjects greater than or equal to 18 years,
  • Subjects currently on oral vitamin K antagonist (VKA) therapy,
  • An urgent surgical procedure is required within 24 hours of the start of investigational medicinal product (IMP),
  • Due to the nature of the procedure, withdrawal of oral VKA therapy and infusion of plasma are also indicated to reverse the VKA effect,
  • INR greater than or equal to 2 within 3 hours before start of IMP,
  • Informed consent has been obtained.

You may not qualify if:

  • Subjects requiring urgent surgical procedures where according to the surgeon's clinical judgment, an accurate estimate of blood loss is not possible (e.g., ruptured aneurysm),
  • Subjects for whom administration of intravenous vitamin K and vitamin K antagonists withdrawal alone can adequately correct the subject's coagulopathy before initiation of the urgent surgical procedure,
  • Administration of intravenous vitamin K more than 3 hours or administration of oral vitamin K more than 6 hours prior to infusion of IMP,
  • Subjects in whom lowering INR within normal range may present an unacceptable risk for a thromboembolic complication where the INR goal is to lower but not normalize the INR because of risk of a procedure-associated stroke,
  • Subjects, who despite medical management that includes close monitoring and diuretics, may not, by investigator assessment, tolerate the total volume of IMP required by the protocol,
  • Expected need for platelet transfusions or desmopressin before Day 10,
  • Acute trauma for which reversal of vitamin K antagonists alone would not be expected to control or resolve an acute bleeding complication and/or control the acute bleeding event,
  • Unfractionated or low molecular weight heparin use within 24 hours before randomization or potential need before completion of the procedure,
  • History of thromboembolic event, myocardial infarction, unstable angina pectoris, critical aortic stenosis, cerebral vascular accident, transient ischemic attack, severe peripheral vascular disease, disseminated intravascular coagulation within 3 months of enrollment,
  • Reversal of VKA therapy alone may not resolve the coagulopathy (eg, receiving a potent anti-platelet agent, i.e., clopidogrel or prasugrel, or advanced liver disease),
  • Known history of antiphospholipid antibody syndrome or lupus anticoagulant antibodies,
  • Suspected or confirmed serious viral or bacterial infection, e.g., meningitis, or sepsis at time of enrollment,
  • 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,
  • Presence or history of hypersensitivity to components of the study medication,
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (30)

Study Site

Newark, Delaware, 19718, United States

Location

Study site

Lexington, Kentucky, 40536, United States

Location

Study Site

Boston, Massachusetts, 02114, United States

Location

Study Site

Duluth, Minnesota, 55805, United States

Location

Study Site

Minneapolis, Minnesota, 55415, United States

Location

Study Site

Albuquerque, New Mexico, 87131, United States

Location

Study Site

Rochester, New York, 14642, United States

Location

Study Site

Winston-Salem, North Carolina, 27157, United States

Location

Study Site

Philadelphia, Pennsylvania, 19107, United States

Location

Study Site

West Reading, Pennsylvania, 19611, United States

Location

Study Site

Wilkes-Barre, Pennsylvania, 18711, United States

Location

Study Site

Memphis, Tennessee, 38163, United States

Location

Study Site

Austin, Texas, 78701, United States

Location

Study site

Bryan, Texas, 77802, United States

Location

Study Site

El Paso, Texas, 79905, United States

Location

Study Site

Houston, Texas, 77030, United States

Location

Study Site 1

Minsk, Belarus

Location

Study Site 2

Minsk, Belarus

Location

Study Site

Rousse, 7002, Bulgaria

Location

Study Site 4

Sofia, 1606, Bulgaria

Location

Study Site

Varna, 9010, Bulgaria

Location

Study Site

Beirut, 2833-7401, Lebanon

Location

Study Site

Saida, 652, Lebanon

Location

Study Site

Timișoara, 300736, Romania

Location

Study Site 2

Barnaul, 656038, Russia

Location

Study Site

Kazan', 420012, Russia

Location

Study Site 1

Moscow, 105203, Russia

Location

Study Site 2

Moscow, 125206, Russia

Location

Study Site

Novosibirsk, 630051, Russia

Location

Study Site

Saint Petersburg, 192242, Russia

Location

Related Publications (2)

  • Goldstein JN, Refaai MA, Milling TJ Jr, Lewis B, Goldberg-Alberts R, Hug BA, Sarode R. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet. 2015 May 23;385(9982):2077-87. doi: 10.1016/S0140-6736(14)61685-8. Epub 2015 Feb 27.

    PMID: 25728933RESULT

  • Refaai MA, Goldstein JN, Lee ML, Durn BL, Milling TJ Jr, Sarode R. Increased risk of volume overload with plasma compared with four-factor prothrombin complex concentrate for urgent vitamin K antagonist reversal. Transfusion. 2015 Nov;55(11):2722-9. doi: 10.1111/trf.13191. Epub 2015 Jul 1.

    PMID: 26135740DERIVED

MeSH Terms

Conditions

Hemophilia BHemostatic Disorders

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, InheritedBlood Coagulation DisordersHematologic DiseasesHemic and Lymphatic DiseasesCoagulation Protein DisordersHemorrhagic DisordersGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGenetic Diseases, X-LinkedVascular DiseasesCardiovascular Diseases

Results Point of Contact

Title
Clinical Trial Disclosure Manager
Organization
CSL Behring
clinicaltrials@cslbehring.com
Use email contact

Study Officials

  • Program Director, Clinical R&D

    CSL Behring

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 4, 2008

First Posted

December 5, 2008

Study Start

February 1, 2009

Primary Completion

November 1, 2012

Study Completion

February 1, 2013

Last Updated

April 6, 2015

Results First Posted

February 25, 2014

Record last verified: 2014-03

Locations

US(16)RU(6)RO(1)BU(3)BE(2)LE(2)