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Blood Cancer J. 2018 Jun 1;8(6):49. doi: 10.1038/s41408-018-0078-3.

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.

Author information

1
Institute of Hematology, Catholic University School of Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. valerio.destefano@unicatt.it.
2
Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
3
Hematology Department, Ospedale San Bortolo, Vicenza, Italy.
4
Institute of Hematology, Catholic University School of Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
5
Unit of Hematology, Department of Oncology, University of Torino, Torino, Italy.
6
Department of Medicine-DIMED, University of Padova, Padova, Italy.
7
Hematology Division, Ospedale San Gerardo, ASST Monza, Monza, Italy.
8
Hematology Division, IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation and University of Milan, Milan, Italy.
9
Monzino Cardiology Center, IRCCS, Milano, Italy.
10
Hematology Department, S. Spirito Hospital, Pescara, Italy.
11
Hematology Division, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
12
Institute of Hematology "L. and A. Seràgnoli", S. Orsola-Malpighi Hospital, Bologna, Italy.
13
CRIMM-Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, and Department Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.
14
Department of Oncology and Hemato-oncology, University of Milan, Milano, Italy.
15
Department of Emergency and Organ Transplantation (D.E.T.O), Hematology Section, University of Bari, Bari, Italy.
16
Fondazione Progetto Ematologia, Vicenza, Italy.

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.

PMID:
29880847
PMCID:
PMC5992153
DOI:
10.1038/s41408-018-0078-3
[Indexed for MEDLINE]
Free PMC Article

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