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

Rush

Status

Completed

Conditions

Hemorrhage

Treatments

Drug: fixed-dose activated prothrombin complex concentrate

Drug: variable-dose inactivated prothrombin complex concentrate

Study type

Observational

Funder types

Other

Identifiers

NCT02565836

15092404

Details and patient eligibility

About

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.

Full 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.

Enrollment

342 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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