TY - JOUR
T1 - Downstream or upstream administration of P2Y12 receptor blockers in non-ST elevated acute coronary syndromes
T2 - study protocol for a randomized controlled trial
AU - Tarantini, Giuseppe
AU - Mojoli, Marco
AU - Varbella, Ferdinando
AU - Caporale, Roberto
AU - Rigattieri, Stefano
AU - Andò, Giuseppe
AU - Cirillo, Plinio
AU - Pierini, Simona
AU - Santarelli, Andrea
AU - Sganzerla, Paolo
AU - De Cesare, Nicoletta
AU - Limbruno, Ugo
AU - Lupi, Alessandro
AU - Ricci, Roberto
AU - Cernetti, Carlo
AU - Favero, Luca
AU - Saia, Francesco
AU - Roncon, Loris
AU - Gasparetto, Valeria
AU - Ferlini, Marco
AU - Ronco, Federico
AU - Ferri, Luca
AU - Trabattoni, Daniela
AU - Russo, Alessandra
AU - Guiducci, Vincenzo
AU - Penzo, Carlo
AU - Tarantino, Fabio
AU - Mauro, Ciro
AU - Marchese, Alfredo
AU - Castiglioni, Battistina
AU - La Manna, Alessio
AU - Martinato, Matteo
AU - Gregori, Dario
AU - Angiolillo, Dominick J.
AU - Musumeci, Giuseppe
N1 - Funding Information:
S.R. reports a consulting fee from Astra Zeneca and a speaker’s fee from Eli Lilly; M.F. reports individual payment as consultant, for advisory board, or as a speaker at scientific congresses from Astra Zeneca, Eli Lilly, Chiesi Farmaceutici, Bayer, Sanofi, and Boehringer-Ingelheim; R.C. reports an advisory board fee from Astra Zeneca; F.S. reports speaker’s fees from Astra Zeneca and Daiichi Sankyo; F.V. reports consulting fees/honoraria from Astra Zeneca, Daiichi Sankyo, Bayer, Pfizer, Boehringer, Servier, Amgen, Sanofi, Piam, Alvi Medica, Teleflex, and Stenty. D.J.A. declares that he has received consulting fees or honoraria from Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company and has received payments for participation in review activities from CeloNova and St Jude Medical. D.J.A. also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, and Renal Guard Solutions; in addition, D.J.A. is recipient of a funding from the Scott R. MacKenzie Foundation and the NIH/NCATS Clinical and Translational Science Award to the University of Florida UL1 TR000064 and NIH/NHGRI U01 HG007269. M.M. reports speaker’s fees from Astra Zeneca, Daiichi Sankyo, and Chiesi Farmaceutici, and that his institution has received an unconditioned research grant from Chiesi Farmaceutici. The other authors report no conflicts of interest.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Background: The optimal timing to administer a P2Y12 inhibitor in patients presenting with a non-ST elevation acute coronary syndrome remains a topic of debate. Pretreatment with ticagrelor before coronary anatomy is known as a widely adopted strategy. However, there is poor evidence on how this compares with administration of a P2Y12 inhibitor after defining coronary anatomy (i.e., downstream administration). Moreover, there are limited head-to-head comparisons of the two P2Y12 inhibitors—ticagrelor and prasugrel—currently recommended by the guidelines. Study design: DUBIUS is a phase 4, multicenter, parallel-group, double randomized study conducted in NSTE-ACS patients designed to compare a pretreatment strategy (including only ticagrelor) versus a downstream strategy (including prasugrel or ticagrelor) and to compare downstream prasugrel with downstream ticagrelor. A total of 2520 patients will be randomly assigned to pretreatment with ticagrelor or to no pretreatment. The PCI group of the downstream arm will be further randomized to receive prasugrel or ticagrelor. The two primary hypotheses are that the downstream strategy is superior to the upstream strategy and that downstream ticagrelor is non-inferior to downstream prasugrel, both measured by the incidence of a composite efficacy and safety endpoint of death from vascular causes, non-fatal MI, or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4, and 5 bleedings. Conclusions: The DUBIUS study will provide important evidence related to the benefits and risks of pretreatment with ticagrelor compared with a strategy of no pretreatment. Moreover, the clinical impact of using downstream ticagrelor compared with downstream prasugrel will be assessed. Trial registration: ClinicalTrials.gov NCT02618837. Registered on 1 December 2015.
AB - Background: The optimal timing to administer a P2Y12 inhibitor in patients presenting with a non-ST elevation acute coronary syndrome remains a topic of debate. Pretreatment with ticagrelor before coronary anatomy is known as a widely adopted strategy. However, there is poor evidence on how this compares with administration of a P2Y12 inhibitor after defining coronary anatomy (i.e., downstream administration). Moreover, there are limited head-to-head comparisons of the two P2Y12 inhibitors—ticagrelor and prasugrel—currently recommended by the guidelines. Study design: DUBIUS is a phase 4, multicenter, parallel-group, double randomized study conducted in NSTE-ACS patients designed to compare a pretreatment strategy (including only ticagrelor) versus a downstream strategy (including prasugrel or ticagrelor) and to compare downstream prasugrel with downstream ticagrelor. A total of 2520 patients will be randomly assigned to pretreatment with ticagrelor or to no pretreatment. The PCI group of the downstream arm will be further randomized to receive prasugrel or ticagrelor. The two primary hypotheses are that the downstream strategy is superior to the upstream strategy and that downstream ticagrelor is non-inferior to downstream prasugrel, both measured by the incidence of a composite efficacy and safety endpoint of death from vascular causes, non-fatal MI, or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4, and 5 bleedings. Conclusions: The DUBIUS study will provide important evidence related to the benefits and risks of pretreatment with ticagrelor compared with a strategy of no pretreatment. Moreover, the clinical impact of using downstream ticagrelor compared with downstream prasugrel will be assessed. Trial registration: ClinicalTrials.gov NCT02618837. Registered on 1 December 2015.
KW - Bleeding
KW - Ischemia
KW - Non-ST elevation acute coronary syndrome
KW - Oral P2Y inhibitors
KW - Randomized clinical trial
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UR - http://www.scopus.com/inward/citedby.url?scp=85096526422&partnerID=8YFLogxK
U2 - 10.1186/s13063-020-04859-1
DO - 10.1186/s13063-020-04859-1
M3 - Article
C2 - 33234137
AN - SCOPUS:85096526422
VL - 21
JO - Trials
JF - Trials
SN - 1745-6215
IS - 1
M1 - 966
ER -