PB1061 - A phase 3 trial of TAK-330 (4-factor prothrombin complex concentrate [4F-PCC]) vs standard-of-care 4F-PCCs for FXa inhibitor-induced anticoagulation reversal before urgent surgery/invasive procedure

Background: Prothrombin complex concentrates (PCCs) have not been studied prospectively in a randomized, clinical trial of patients requiring reversal of an activated factor X (FXa) inhibitor prior to urgent surgery.

Aims: To evaluate the efficacy and safety of a 4-factor PCC (4F-PCC, [TAK-330, Takeda]), versus current standard-of-care 4F-PCCs, for the reversal of FXa inhibitor-induced anticoagulation in patients who require urgent surgery/invasive procedures.

Methods: This phase 3, randomized, multicenter, open-label, adaptive group sequential, noninferiority study (NCT05156983) is actively enrolling. It aims to recruit 328 patients (≥18 years old) currently receiving an oral FXa inhibitor (rivaroxaban, apixaban, or edoxaban) who require urgent surgery/invasive procedures with a high-risk of intraoperative bleeding within 15 hours of their last FXa inhibitor dose. Patients will be randomized 1:1 to receive TAK-330 or an active comparator standard-of-care 4F-PCC before their procedure; the total dose should be ≤50 IU/kg (≤5000 IU/patient). The study design is shown in Fig. 1. The primary endpoint is the intraoperative efficacy based on the four-point intraoperative hemostatic efficacy scale at the end of the procedure (Fig. 2). The key secondary endpoint is the postoperative hemostatic efficacy assessed at 24±4 hours after study drug infusion. Additional secondary endpoints are the use of blood products or non-study hemostatic agents for bleeding control up to 24±4 hours after study drug infusion; occurrence of thrombotic events, treatment-emergent adverse events, serious adverse events and adverse events of special interest; and occurrence of all-cause deaths (all within 30±3 days of surgery/invasive procedure or study completion). This study has received institutional review board approval and is funded by Takeda Development Center Americas, Inc.

Results: Not applicable.

Conclusion(s): Results from this study will provide efficacy and safety data on TAK-330 versus standard-of-care 4F-PCCs for the reversal of direct oral FXa inhibitor-induced anticoagulation in patients requiring urgent surgery/invasive procedures.