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
|Condition or disease||Intervention/treatment|
|Hemorrhage||Drug: fixed-dose activated prothrombin complex concentrate Drug: variable-dose inactivated prothrombin complex concentrate|
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.
|Study Type :||Observational|
|Actual Enrollment :||342 participants|
|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|
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
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
- 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.
- 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.
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
|Principal Investigator:||Gary D Peksa, PharmD||Rush University Medical Center|
|Principal Investigator:||Robert Mokszycki, PharmD||Advocate Christ Medical Center|