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., Competing Interests: I.M. reports an independent research grant to the sponsor (AP-HP) from BMS/Pfizer. I.M. has received a research grant from Leo Pharma, has been a speaker for BMS and Leo Pharma, and has participated in advisory boards for BMS and Bayer. G.A.: no disclosure was declared by the author. C.A. has received honoraria for lectures from Bayer, BKS, Pfizer, Sanofi, and Daiichi Sankyo, and has participated in advisory boards for Bayer, BMS, Pfizer, and Sanofi. C.B. has received consulting fees/honoraria from Bayer Healthcare, Daiichi Sankyo, and BMS. A.B. has nothing to disclose. M.C. reports research funding from BMS, Pfizer, and Leo Pharma, and honoraria from BMS, Pfizer, Sanofi, Bayer, Leo Pharma, Servier, and Valeo; all payments were made to the institution. C.C. has received consulting fees from Leo Pharma. A.T.C.: no disclosure was declared by the author. P.G. has received honoraria and support for attending meetings and/or travel from Leo Pharma and Bayer. M.V.H. reports grants from ZonMW Dutch Healthcare Fund, and grants and personal fees to the hospital from Boehringer Ingelheim, BMS/Pfizer, Bayer Healthcare, Aspen, and Daiichi Sankyo, all outside the submitted work. F.A.K. reports research grants from Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, MSD, The Netherlands Organization for Health Research and Development, Actelion, the Dutch Heart Foundation, and the Dutch Thrombosis Association, all outside the submitted work. J.J.L.-N. has received honoraria for: lectures from Bayer, Pfizer and Rovi; educational events from Leo Pharma; lectures and support for attending meetings and travel from Bayer, Boehringer Ingelheim, BMS, Pfizer, Leo Pharma, Rovi, and Sanofi; and advisory board participation from Pfizer and Techdow. A.M. has received honoraria from Bayer, BMS, Leo Pharma, Rovi, and Pfizer, and support for attending meetings and/or travel from Bayer and BMS, and has participated in a data safety monitoring board or an advisory board for Bayer, BMS, and Leo Pharma. D.M. has received consulting fees from Leo Pharma, Pfizer, and BMS, and honoraria and support for attending meetings and/or travel from Leo Pharma and Pfizer. O.M. has received consulting fees from AstraZeneca, Blueprint Medicines, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Ipsen, Merck Sharpe & Dohme, Pfizer, Roche, Servier, and Vifor Pharma, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Blueprint Medicines, Eli-Lilly, Pfizer, Roche, and support for attending meetings and/or travel from Amgen and Roche, and has participated on a data safety monitoring board or advisory board for Blueprint Medicines, Boehringer-Ingelheim; and holds stock or stock options in Amplitude Surgical and Ipsen Transgene. M.M. has received an unrestricted grant for research from Sanofi, Leo Pharma, and Rovi, consulting fees from Sanofi and Bristol, and honoraria for lectures from Sanofi and Pfizer. M.R. has received honoraria for lectures from Bayer, Pfizer, and Biomérieux. C.M.S. has participated in a data safety monitoring board for the API-CAT study. K.S. has received personal fees from Roche, BMS, and MSD, and institutional fees from Amgen. S.S. has received honoraria for lectures from Bayer, BMS, Pfizer, Angelini, Janssen-Cilag, and Roche, and support for attending meetings and/or travel from BMS. A.T. has received consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and participated on an advisory board for Bayer and Pfizer. P.V. is co-holder of the Bayer Chair in Cardiovascular Medicine at the University of Leuven. He has received consulting fees from Bayer, Daiichi Sankyo, Portola, and Anthos Pharmaceuticals, and honoraria from Bayer, Daiichi Sankyo, BMS, Pfizer, Boehringer, and Leo Pharma. E.V. has contracts for consulting in statistics with Pfizer, Novartis, Boehringer, Hexacath, Amgen, and Abbott. He has received fees for consulting in statistics from Pfizer, Novartis, Boehringer, Hexacath, Amgen, and Abbott, and honoraria for lectures on statistics from Amgen. T.-F.W. has received a research grant from Leo Pharma, and has participated in advisory boards for Pfizer and Servier. G.M. is deceased. S.L. has received grants from Leo Pharma, grants and consulting fees from Bayer Healthcare, and speaker fees from BMS, Pfizer, Merck Serono. The other authors report no conflicts of interest., (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/).)