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Fixed-dose Activated Versus Variable-dose Inactivated Prothrombin Complex Concentrate for Warfarin-associated Major Bleed

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ClinicalTrials.gov Identifier: NCT02565836
Recruitment Status : Completed
First Posted : October 1, 2015
Last Update Posted : October 25, 2017
Sponsor:
Collaborator:
Advocate Health Care
Information provided by (Responsible Party):
Rush University Medical Center

Brief Summary:
This study aims to assess a fixed-dose regimen of activated prothrombin complex concentrate (FEIBA VH, Baxter) versus the variable, manufacturer recommended, dose regimen of inactivated prothrombin complex concentrate (Kcentra, CSL Behring) for reversal of warfarin-associated major hemorrhage.

Condition or disease Intervention/treatment
Hemorrhage Drug: fixed-dose activated prothrombin complex concentrate Drug: variable-dose inactivated prothrombin complex concentrate

Detailed Description:

Warfarin, a vitamin K antagonist (VKA), is the most frequently prescribed oral anticoagulant. Warfarin-associated major hemorrhage occurs at a rate of 1.7% to 3.4% in routine clinical practice and warrants rapid reversal of anticoagulation by correcting supratherapeutic international normalized ratio (INR) values.

Warfarin inhibits synthesis of vitamin K dependent coagulation factors II, VII, IX, and X, and strategies for reversal of warfarin-associated coagulopathy are aimed at restoring deficient factors. Four-factor prothrombin complex concentrates (PCCs) contain the coagulation factors which warfarin inhibits and are an attractive option for rapid reversal due to ease of reconstitution and no requirement for blood-type matching.

Manufacturer dosing recommendations exist for PCCs based on patient weight, baseline INR, and target INR, but studies have suggested fixed dosing strategies in an effort to determine the most efficacious dose for VKA-reversal while sparing adverse events. These studies have also utilized different PCC formulations, with some studies utilizing 4-factor activated PCC (aPCC), which denotes product containment of factor VII in an activated state.

In the United States, product availability is limited to a single 4-factor aPCC (FEIBA VH, Baxter) indicated for hemophilia patients with inhibitors and a single 4-factor inactivated PCC (Kcentra, CSL Behring) approved for VKA-reversal. Various institutions choose to utilize off-label fixed dosing strategies of 4-factor aPCC in an effort to administer the lowest possible dose to reverse VKAs, while others utilize manufacturer recommended dosing of 4-factor inactivated PCC.


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Study Type : Observational
Actual Enrollment : 342 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Reversal of Warfarin-associated Major Hemorrhage: a Multicenter, Retrospective Cohort Study of Fixed-dose Activated (FEIBA VH) Versus Variable-dose Inactivated (Kcentra) Prothrombin Complex Concentrate
Study Start Date : October 2015
Actual Primary Completion Date : September 30, 2016
Actual Study Completion Date : September 30, 2016


Group/Cohort Intervention/treatment
fixed-dose aPCC
Patients receiving fixed-dose activated prothrombin complex concentrate (FEIBA VH) for reversal of warfarin-associated major hemorrhage.
Drug: fixed-dose activated prothrombin complex concentrate

FEIBA VH 500 units IV one time for INR less than 5. FEIBA VH 1000 units IV one time for INR greater than 5.

Check INR after infusion and may repeat dose if INR still elevated

Other Names:
  • FEIBA
  • FEIBA VH

variable-dose PCC
Patients receiving vairable-dose inactivated prothrombin complex concentrate (Kcentra) for reversal of warfarin-associated major hemorrhage.
Drug: variable-dose inactivated prothrombin complex concentrate

Kcentra 25 units/kg IV one time for INR less than 4. Kcentra 35 units/kg IV one-time for INR 4 to 6. Kcentra 50 units/kg IV one-time for INR greater than 6.

Check INR after infusion and may repeat dose if INR still elevated.

Other Name: Kcentra




Primary Outcome Measures :
  1. Achievement of INR less than or equal to 1.5 [ Time Frame: 60 minutes ]
    The number of patients achieving a goal INR of less than or equal to 1.5 within 60 minutes following administration of 4-factor fixed-dose aPCC (FEIBA VH) versus variable-dose inactivated PCC (Kcentra) for reversal of warfarin-associated major hemorrhage.


Secondary Outcome Measures :
  1. Incidence of mortality or thrombotic events [ Time Frame: 30 days ]
    Incidence of mortality, deep vein thrombosis, pulmonary embolism, myocardial infarction, and ischemic cerebrovascular events within 30 days following administration of 4-factor fixed-dose aPCC (FEIBA VH) or variable-dose inactivated PCC (Kcentra) for reversal of warfarin-associated major hemorrhage.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients administered a prothrombin complex concentrate as part of routine care for INR normalization due to a major bleed will be assessed for inclusion.
Criteria

Inclusion Criteria:

  • Pre-treatment INR lab value greater than 1.5
  • Receipt of treatment with a 4-factor PCC for INR normalization due to warfarin-associated major hemorrhage

Exclusion Criteria:

  • Patients treated with a PCC for an urgent invasive procedure without active hemorrhage
  • Patients treated with PCC not taking a VKA
  • Unavailable pre- or post-treatment INR lab values
  • Pregnant patients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02565836


Sponsors and Collaborators
Rush University Medical Center
Advocate Health Care
Investigators
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Principal Investigator: Gary D Peksa, PharmD Rush University Medical Center
Principal Investigator: Robert Mokszycki, PharmD Advocate Christ Medical Center

Publications:
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Responsible Party: Rush University Medical Center
ClinicalTrials.gov Identifier: NCT02565836     History of Changes
Other Study ID Numbers: 15092404
First Posted: October 1, 2015    Key Record Dates
Last Update Posted: October 25, 2017
Last Verified: October 2017
Keywords provided by Rush University Medical Center:
Vitamin K 1
prothrombin complex concentrates
warfarin
Additional relevant MeSH terms:
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Hemorrhage
Pathologic Processes
Warfarin
Thrombin
Anti-inhibitor coagulant complex
Anticoagulants
Hemostatics
Coagulants