TY - JOUR
T1 - COMPARison of pre-hospital CRUSHed vs. uncrushed Prasugrel tablets in patients with STEMI undergoing primary percutaneous coronary interventions
T2 - Rationale and design of the COMPARE CRUSH trial: Study Design Compare Crush Trial
AU - Vlachojannis, Georgios J
AU - Vogel, Rosanne F
AU - Wilschut, Jeroen M
AU - Lemmert, Miguel E
AU - Delewi, Ronak
AU - Diletti, Roberto
AU - van Vliet, Ria
AU - van der Waarden, Nancy
AU - Nuis, Rutger-Jan
AU - Paradies, Valeria
AU - Alexopoulos, Dimitrios
AU - Zijlstra, Felix
AU - Montalescot, Gilles
AU - Angiolillo, Dominick J
AU - Krucoff, Mitchell W
AU - Van Mieghem, Nicolas M
AU - Smits, Pieter C
N1 - Funding Information:
The COMPARE CRUSH trial is supported by Unrestricted Research Grants from Shanghai MicroPort Medical and Daiichi-Sankyo.
Funding Information:
The COMPARE CRUSH study is an investigator initiated trial. The study sponsor is Maasstad Hospital. The trial is funded by grants from MicroPort and Daiichi-Sankyo. Solely the authors are responsible for the design and conduct of the study and all study analyses. The funding sources had no role in the design of this study, and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results. None of the industry partners reviewed the manuscript during its development or were allowed to make suggestions.
Funding Information:
We would like to thank the team of the regional ambulance service ?AmbulanceZorg Rotterdam-Rijnmond? and their medical director Marileen Biekhart. Further we would like to thank the regional cardiology association ?Cardiologen Club Rijnmond?. Also we would like to thank the members of the data monitoring and safety board Freek W.A. Verheugt, Jan G. P. Tijssen, and Michiel Voskuil? the members of the clinical event adjudication committee Karel T. Koch and Martijn Meuwissen? the members of the STEMI adjudication committee Freek Nijhoff and Maik Grundeken. Moreover, we would like to thank Claudia Vliet, Arno Ruiter, Rachel van Dam, and Jacqueline Rijssemus for clinical data acquisition. Finally, we would like to thank our industry partners Ming Zheng (MicroPort Medical Group), Sandy Lee (Daiichi Sankyo), Kristel R?lle & Vera de Groot (Werfen-Instrumentation Laboratory), John Uiters (Medwave), Uwe Gladbach (ClinFlows), Steve Bierman (SyringeCrusher), as well as Martino Vaglio & Fabio Badilini (AMPS LLC).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - BACKGROUND: Dual antiplatelet therapy constitutes the cornerstone of medical treatment in patients with ST elevation myocardial infarction (STEMI). However, oral antiplatelet agents, such as prasugrel or ticagrelor, are characterized by slow gastrointestinal drug absorption in the acute phase of STEMI, leading to decreased bioavailability and therefore delayed onset of platelet inhibition. Evidence suggests that administration of crushed tablets of the P2Y12 inhibitor prasugrel improves drug absorption and achieves earlier antiplatelet effects in STEMI patients undergoing primary percutaneous coronary intervention (PCI). However, the clinical implications of these pharmacokinetic and pharmacodynamic findings are unknown.HYPOTHESIS: The present study is designed to test the hypothesis that patients presenting with STEMI planned for primary PCI will have improved markers of optimal reperfusion and clinical outcomes by prehospital administration of crushed tablets of prasugrel loading dose.STUDY DESIGN: COMPARE CRUSH (NCT03296540) is a randomized trial in a regionally organized ambulance care setting evaluating the efficacy and safety of pre-hospital loading dose with prasugrel crushed tablets versus integral tablets in approximately 674 patients presenting with STEMI planned for primary PCI. The independent primary endpoints are percentage of patients reaching thrombolysis in myocardial infarction (TIMI) flow grade 3 in the infarct-related artery at initial angiography, or achieving ≥70% ST-segment elevation resolution at 1 hour post-PCI. Secondary clinical endpoints are death, myocardial infarction, revascularization, and stent thrombosis followed up to 1 year. Moreover, the primary safety endpoint is bleeding events assessed at 48 hours.CONCLUSIONS: The COMPARE CRUSH trial will assess whether prehospital administration of loading dose prasugrel in form of crushed tablets - which is expected to provide faster platelet inhibition compared to standard treatment with integral tablets - results in improved reperfusion and clinical outcomes. RCT# NCT03296540.
AB - BACKGROUND: Dual antiplatelet therapy constitutes the cornerstone of medical treatment in patients with ST elevation myocardial infarction (STEMI). However, oral antiplatelet agents, such as prasugrel or ticagrelor, are characterized by slow gastrointestinal drug absorption in the acute phase of STEMI, leading to decreased bioavailability and therefore delayed onset of platelet inhibition. Evidence suggests that administration of crushed tablets of the P2Y12 inhibitor prasugrel improves drug absorption and achieves earlier antiplatelet effects in STEMI patients undergoing primary percutaneous coronary intervention (PCI). However, the clinical implications of these pharmacokinetic and pharmacodynamic findings are unknown.HYPOTHESIS: The present study is designed to test the hypothesis that patients presenting with STEMI planned for primary PCI will have improved markers of optimal reperfusion and clinical outcomes by prehospital administration of crushed tablets of prasugrel loading dose.STUDY DESIGN: COMPARE CRUSH (NCT03296540) is a randomized trial in a regionally organized ambulance care setting evaluating the efficacy and safety of pre-hospital loading dose with prasugrel crushed tablets versus integral tablets in approximately 674 patients presenting with STEMI planned for primary PCI. The independent primary endpoints are percentage of patients reaching thrombolysis in myocardial infarction (TIMI) flow grade 3 in the infarct-related artery at initial angiography, or achieving ≥70% ST-segment elevation resolution at 1 hour post-PCI. Secondary clinical endpoints are death, myocardial infarction, revascularization, and stent thrombosis followed up to 1 year. Moreover, the primary safety endpoint is bleeding events assessed at 48 hours.CONCLUSIONS: The COMPARE CRUSH trial will assess whether prehospital administration of loading dose prasugrel in form of crushed tablets - which is expected to provide faster platelet inhibition compared to standard treatment with integral tablets - results in improved reperfusion and clinical outcomes. RCT# NCT03296540.
UR - http://www.scopus.com/inward/record.url?scp=85082697883&partnerID=8YFLogxK
U2 - 10.1016/j.ahj.2020.03.005
DO - 10.1016/j.ahj.2020.03.005
M3 - Article
C2 - 32272255
SN - 0002-8703
VL - 224
SP - 10
EP - 16
JO - American Heart Journal
JF - American Heart Journal
ER -