A phase 3 noninferiority trial to evaluate the efficacy and safety of TAK-330 (4-factor prothrombin complex concentrate [4F-PCC]) versus standard-of-care 4F-PCC for the reversal of factor Xa inhibitor-induced anticoagulation before urgent surgery or an invasive procedure

Abstract text (incl. references and figure legends)

Introduction

This study aims to evaluate the efficacy and safety of TAK-330 (4-factor prothrombin complex concentrate [4F-PCC], Takeda), versus current standard-of-care (SOC) 4F-PCCs, for the reversal of factor Xa (FXa) inhibitor-induced anticoagulation in patients who require urgent surgery/invasive procedure.

Materials & Methods

This phase 3, randomized, multicenter, open-label, adaptive group sequential, noninferiority study aims to recruit 328 patients (≥18 years old) currently receiving an oral FXa inhibitor (rivaroxaban, apixaban or edoxaban) who require urgent surgery/invasive procedure with a high-risk of intraoperative bleeding within 15 hours after their last FXa inhibitor dose. Patients will be randomized 1:1 to receive TAK-330 or an active comparator SOC 4F-PCC before their procedure; the total dose should be ≤50 IU/kg (≤5000 IU/patient). The study design is shown in Fig. 1. Key exclusion criteria are acute major bleeding and a recent history of thromboembolism or disseminated intravascular coagulation. The primary endpoint is the intraoperative efficacy based on the Four-Point Intraoperative Hemostatic Efficacy Scale at the end of the procedure. The key secondary endpoint is the postoperative hemostatic efficacy assessed at 24±4 hours after study drug infusion. Additional secondary endpoints are use of blood products or nonstudy 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 post surgery/invasive procedure or study completion).

Results

Not applicable.

Conclusions

Results from this study will provide efficacy and safety data on TAK-330 versus SOC 4F-PCCs for the reversal of direct oral FXa inhibitor-induced anticoagulation in patients requiring urgent surgery/invasive procedure.

References

ClinicalTrials.gov: NCT05156983

EudraCT: 2021-004138-12

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Conflicts of interest

MKK is an employee of Takeda Pharmaceuticals International AG and a stockholder of Takeda Pharmaceutical Company Limited.

HK is a contractor of Takeda Development Center Americas, Inc.

JG is an employee of Massachusetts General Hospital and has received research support from Octapharma, Pfizer and Takeda, and has provided consulting services for AstraZeneca, Cayuga Biotech, CSL Behring and Ncontrol.

JL serves on steering committees for Merck, Octapharma and Werfen.

HA is an employee of Massachusetts General Hospital and Takeda Development Center Americas, Inc., as well as a stockholder of Takeda Pharmaceutical Company Limited.

This study was funded by Takeda Development Center Americas, Inc. Medical writing support was provided by Jessica Boles, PhD, of PharmaGenesis London, London, UK, and funded by Takeda Pharmaceuticals International AG.