The Aspirin Regimens in Essential Thrombocythemia (ARES) phase II randomized trial design: Implementation of the serum thromboxane B2 assay as an evaluation tool of different aspirin dosing regimens in the clinical setting

• DOI: 10.1038/s41408-018-0078-3
• Publication Date: 2018-06-01T11:27:57Z
• Authors: Valerio De Stefano; Bianca Rocca; Alberto Tosetto; Denise Soldati; Giovanna Petrucci; Eloise Beggiato; Irene Bertozzi; Silvia Betti; Giuseppe Carli; Monica Carpenedo; Daniele Cattaneo; Viviana Cavalca; Alfredo Dragani; Elena Elli; Guido Finazzi; Alessandra Iurlo; Giuseppe Lanzarone; Laura Lissandrini; Francesca Palandri; Chiara Paoli; Alessandro Rambaldi; Paola Ranalli; Maria Luigia Randi; Alessandra Ricco; Elena Rossi; Marco Ruggeri; Giorgina Specchia; Andrea Timillero; Linda Turnu; Nicola Vianelli; Alessandro M. Van...; Francesco Rodeghiero; Carlo Patrono
• Keywords: Male; 610; Aspirin Regimens, Essential Thrombocythemia, ARES, thromboxane B2; Article; 03 medical and health sciences; 0302 clinical medicine; Clinical Protocols; Aspirin / administration & dosage, Biomarkers, Clinical Protocols, Disease Management, Female, Humans, Male, Patient Selection, Platelet Aggregation Inhibitors / administration & dosage, Research Design, Thrombocythemia, Essential / complications, Thrombocythemia, Essential / diagnosis, Thrombosis / blood, Thrombosis / diagnosis, Thrombosis / etiology, Thrombosis / prevention & control, Thromboxane B2 / blood; 616; Humans; Essential Thrombocythemia; Aspirin; Patient Selection; Disease Management; Thrombosis; Hematology; Hematology; Oncology; 3. Good health; Thromboxane B2; Oncology; Research Design; Female; Biomarkers; Platelet Aggregation Inhibitors; Thrombocythemia, Essential

AbstractOnce-daily (od), low-dose aspirin (75–100 mg) is recommended to reduce the thrombotic risk of patients with essential thrombocytemia (ET). This practice is based on data extrapolated from other high-risk patients and an aspirin trial in polycythemia vera, with the assumption of similar aspirin pharmacodynamics in the two settings. However, the pharmacodynamics of low-dose aspirin is impaired in ET, reflecting accelerated renewal of platelet cyclooxygenase (COX)-1. ARES is a parallel-arm, placebo-controlled, randomized, dose-finding, phase II trial enrolling 300 ET patients to address two main questions. First, whether twice or three times 100 mg aspirin daily dosing is superior to the standard od regimen in inhibiting platelet thromboxane (TX)A2 production, without inhibiting vascular prostacyclin biosynthesis. Second, whether long-term persistence of superior biochemical efficacy can be safely maintained with multiple vs. single dosing aspirin regimen. Considering that the primary study end point is serum TXB2, a surrogate biomarker of clinical efficacy, a preliminary exercise of reproducibility and validation of this biomarker across all the 11 participating centers was implemented. The results of this preliminary phase demonstrate the importance of controlling reproducibility of biomarkers in multicenter trials and the feasibility of using serum TXB2 as a reliable end point for dose-finding studies of novel aspirin regimens.