Extended Anticoagulant Treatment with Full- or Reduced-Dose Apixaban in Patients with Cancer-Associated Venous Thromboembolism: Rationale and Design of the API-CAT Study

Thromb Haemost. 2022 Apr;122(4):646-656. doi: 10.1055/a-1647-9896. Epub 2021 Nov 5.

Abstract

Cancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding. The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5 mg twice daily [bid]) is noninferior to a full-dose regimen of apixaban (5 mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed ≥6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism. API-CAT is an international, randomized, parallel-group, double-blind, noninferiority trial with blinded adjudication of outcome events. Consecutive patients are randomized to receive apixaban 2.5 or 5 mg bid for 12 months. The primary efficacy outcome is a composite of recurrent symptomatic or incidental VTE during the treatment period. The principal safety endpoint is clinically relevant bleeding, defined as a composite of major bleeding or nonmajor clinically relevant bleeding. Assuming a 12-month incidence of the primary outcome of 4% with apixaban and an upper limit of the two-sided 95% confidence interval of the hazard ratio <2.0, 1,722 patients will be randomized, assuming an up to 10% loss in total patient-years (β = 80%; α one-sided = 0.025). This trial has the potential to demonstrate that a regimen of extended treatment for patients with CT beyond an initial 6 months, with a reduced apixaban dose, has an acceptable risk of recurrent VTE recurrence and decreases the risk of bleeding.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Anticoagulants / adverse effects
  • Hemorrhage / epidemiology
  • Humans
  • Neoplasms* / drug therapy
  • Pyrazoles
  • Pyridones / adverse effects
  • Venous Thromboembolism* / diagnosis
  • Venous Thromboembolism* / drug therapy
  • Venous Thromboembolism* / prevention & control

Substances

  • Anticoagulants
  • Pyrazoles
  • Pyridones
  • apixaban

Grants and funding

Funding Funding for the study is provided by the BMS–Pfizer Alliance. Tablets of apixaban are provided by Bristol-Myers Squibb and are packaged under AP-HP's responsibility. Bristol-Myers Squibb and Pfizer did not have any role in the study design, study conduction, data collection, or analysis.