Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12857/115264
Title: 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
Authors: De Stefano, Valerio
Rocca, Bianca
Tosetto, Alberto 
Soldati, Denise
Petrucci, Giovanna
Beggiato, Eloise
Bertozzi, Irene 
Betti, Silvia
Carli, Giuseppe 
Carpenedo, Monica
Cattaneo, Daniele
Cavalca, Viviana
Dragani, Alfredo
Elli, Elena
Finazzi, Guido
Iurlo, Alessandra
Lanzarone, Giuseppe
Lissandrini, Laura 
Palandri, Francesca
Paoli, Chiara
Rambaldi, Alessandro
Ranalli, Paola
Randi, Maria Luigia 
Ricco, Alessandra
Rossi, Elena
Ruggeri, Marco 
Specchia, Giorgina
Timillero, Andrea
Turnu, Linda
Vianelli, Nicola
Vannucchi, Alessandro M
Rodeghiero, Francesco 
Patrono, Carlo
Keywords Plus: LOW-DOSE ASPIRIN;MYELOPROLIFERATIVE NEOPLASMS TRENDS;PLATELET CYCLOOXYGENASE INHIBITION;RISK ESSENTIAL THROMBOCYTHEMIA;WORLD-HEALTH-ORGANIZATION;POLYCYTHEMIA-VERA;SECONDARY PREVENTION;PROSTACYCLIN BIOSYNTHESIS;ANTIPLATELET THERAPY;NONSURGICAL PATIENTS
Mesh headings: Aspirin;Clinical Protocols;Platelet Aggregation Inhibitors;Thrombocythemia, Essential;Thrombosis
Secondary Mesh headings: Biomarkers;Disease Management;Female;Humans;Male;Patient Selection;Research Design;Thromboxane B2
Issue Date: 2018
Publisher: NATURE PUBLISHING GROUP
Journal: Blood cancer journal 
Abstract: 
Once-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.
URI: http://hdl.handle.net/20.500.12857/115264
ISSN: 2044-5385
DOI: 10.1038/s41408-018-0078-3
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