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CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(04): 646-656
DOI: 10.1055/a-1647-9896
Trial Protocol Design Paper

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

Isabelle Mahé 
1   Service de Médecine Interne, Hôpital Louis Mourier, AP-HP, Colombes, France
2   Université de Paris, Paris, France
3   Innovative Therapies in Haemostasis, INSERM UMR_S1140, Paris, France
4   INNOVTE-FCRIN, Saint-Etienne, France
,
Giancarlo Agnelli
5   Internal Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
,
Cihan Ay
6   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
,
Aristotelis Bamias 
7   2nd Propaedeutic Department of Medicine, ATTIKON University Hospital, National & Kapodistrian University of Athens, Athens, Greece
,
Cecilia Becattini
5   Internal Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
,
Marc Carrier
8   Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
,
Céline Chapelle
9   Unité de Recherche Clinique Innovation et Pharmacologie, CHU de Saint-Etienne, Saint-Etienne, France
10   SAINBIOSE INSERM U1059, Université Jean Monnet, Université de Lyon, Saint-Etienne, France
,
Alexander T. Cohen
11   Guy's and St. Thomas' NHS Foundation Trust Hospital, King's College London, London, United Kingdom
,
Philippe Girard
12   Département de Pneumologie, Institut Mutualiste Montsouris, Paris, France
,
Menno V. Huisman
13   Department of Medicine − Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
,
Frederikus A. Klok 
13   Department of Medicine − Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
,
Juan J. López-Núñez
14   Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
15   Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
,
Anthony Maraveyas
16   Queen's Centre for Oncology and Haematology, Hull University Teaching Hospitals NHS Trust, Hull York Medical School, Cottingham, Hull, United Kingdom
,
Didier Mayeur
17   Centre Georges-Francois Leclerc, Dijon, France
,
Olivier Mir
18   Institut Gustave-Roussy, Paris, France
,
Manuel Monreal
14   Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
15   Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
19   Universidad Católica de Murcia, Murcia, Spain
,
Marc Righini
20   Division of Angiology and Hemostasis, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
,
Charles M. Samama
21   Intensive Care and Perioperative Medicine, Department of Anaesthesia, Hôpital Cochin, GHU AP-HP Centre-Université de Paris, Paris, France
,
Kostas Syrigos
22   Department of Medicine, Sotiria General Hospital, Athens School of Medicine, National & Kapodistrian University, Athens, Greece
,
Sebastian Szmit
23   Departments of Pulmonary Circulation, Thromboembolic Diseases, and Cardiology, Centre of Postgraduate Medical Education, European Health Centre, Otwock, Poland
,
Adam Torbicki
23   Departments of Pulmonary Circulation, Thromboembolic Diseases, and Cardiology, Centre of Postgraduate Medical Education, European Health Centre, Otwock, Poland
,
Peter Verhamme 
24   Vascular Medicine and Haemostasis, University Hospitals Leuven, Leuven, Belgium
,
Eric Vicaut
25   URC Lariboisière – Saint-Louis, AP-HP, Université de Paris, Paris, France
,
Tzu-Fei Wang
8   Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
,
Guy Meyer
2   Université de Paris, Paris, France
4   INNOVTE-FCRIN, Saint-Etienne, France
26   Hôpital Européen Georges Pompidou, APHP, Sorbonne Paris Cité, Paris, France
,
Silvy Laporte
4   INNOVTE-FCRIN, Saint-Etienne, France
9   Unité de Recherche Clinique Innovation et Pharmacologie, CHU de Saint-Etienne, Saint-Etienne, France
10   SAINBIOSE INSERM U1059, Université Jean Monnet, Université de Lyon, Saint-Etienne, France
› Author Affiliations 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.
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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.

Keywords

venous thromboembolism - cancer - apixaban - randomized

Supplementary Material



Publication History

Received: 27 May 2021

Accepted: 08 July 2021

Accepted Manuscript online:
17 September 2021

Article published online:
05 November 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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