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

NCT ID: NCT02565836

Last Updated: 2017-10-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

342 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-10-31

Study Completion Date

2016-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hemorrhage

Keywords

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Vitamin K 1 prothrombin complex concentrates warfarin

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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fixed-dose aPCC

Patients receiving fixed-dose activated prothrombin complex concentrate (FEIBA VH) for reversal of warfarin-associated major hemorrhage.

fixed-dose activated prothrombin complex concentrate

Intervention Type DRUG

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

variable-dose PCC

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

variable-dose inactivated prothrombin complex concentrate

Intervention Type DRUG

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.

Interventions

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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

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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FEIBA FEIBA VH Kcentra

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Wake Forest University Health Sciences

OTHER

Sponsor Role collaborator

Rush University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gary D Peksa, PharmD

Role: PRINCIPAL_INVESTIGATOR

Rush University Medical Center

Robert Mokszycki, PharmD

Role: PRINCIPAL_INVESTIGATOR

advocate christ medical center

References

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Junagade P, Grace R, Gover P. Fixed dose prothrombin complex concentrate for the reversal of oral anticoagulation therapy. Hematology. 2007 Oct;12(5):439-40. doi: 10.1080/10245330701448529.

Reference Type BACKGROUND
PMID: 17852462 (View on PubMed)

Wojcik C, Schymik ML, Cure EG. Activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for the reversal of warfarin-induced coagulopathy. Int J Emerg Med. 2009 Nov 26;2(4):217-25. doi: 10.1007/s12245-009-0125-8.

Reference Type BACKGROUND
PMID: 20436891 (View on PubMed)

Khorsand N, Veeger NJ, van Hest RM, Ypma PF, Heidt J, Meijer K. An observational, prospective, two-cohort comparison of a fixed versus variable dosing strategy of prothrombin complex concentrate to counteract vitamin K antagonists in 240 bleeding emergencies. Haematologica. 2012 Oct;97(10):1501-6. doi: 10.3324/haematol.2012.063701. Epub 2012 Apr 4.

Reference Type BACKGROUND
PMID: 22491734 (View on PubMed)

Stewart WS, Pettit H. Experiences with an activated 4-factor prothrombin complex concentrate (FEIBA) for reversal of warfarin-related bleeding. Am J Emerg Med. 2013 Aug;31(8):1251-4. doi: 10.1016/j.ajem.2013.05.008. Epub 2013 Jun 10.

Reference Type BACKGROUND
PMID: 23763937 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23935011 (View on PubMed)

Other Identifiers

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15092404

Identifier Type: -

Identifier Source: org_study_id