PMID- 32272255 OWN - NLM STAT- MEDLINE DCOM- 20200716 LR - 20200716 IS - 1097-6744 (Electronic) IS - 0002-8703 (Linking) VI - 224 DP - 2020 Jun TI - COMPARison of pre-hospital CRUSHed vs. uncrushed Prasugrel tablets in patients with STEMI undergoing primary percutaneous coronary interventions: Rationale and design of the COMPARE CRUSH trial. PG - 10-16 LID - S0002-8703(20)30079-X [pii] LID - 10.1016/j.ahj.2020.03.005 [doi] 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 P2Y(12) 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. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Vlachojannis, Georgios J AU - Vlachojannis GJ AD - Maasstad Hospital, Rotterdam; University Medical Center Utrecht, Netherlands. Electronic address: g.vlachojannis@umcutrecht.nl. FAU - Vogel, Rosanne F AU - Vogel RF AD - University Medical Center Utrecht, Netherlands. FAU - Wilschut, Jeroen M AU - Wilschut JM AD - Erasmus Medical Center, Rotterdam, Netherlands. FAU - Lemmert, Miguel E AU - Lemmert ME AD - Erasmus Medical Center, Rotterdam, Netherlands. FAU - Delewi, Ronak AU - Delewi R AD - Academic Medical Center Amsterdam, Amsterdam, Netherlands. FAU - Diletti, Roberto AU - Diletti R AD - Erasmus Medical Center, Rotterdam, Netherlands. FAU - van Vliet, Ria AU - van Vliet R AD - Maasstad Hospital, Rotterdam. FAU - van der Waarden, Nancy AU - van der Waarden N AD - Ambulance Zorg Rotterdam-Rijnmond, Rotterdam, Netherlands. FAU - Nuis, Rutger-Jan AU - Nuis RJ AD - Erasmus Medical Center, Rotterdam, Netherlands. FAU - Paradies, Valeria AU - Paradies V AD - Maasstad Hospital, Rotterdam. FAU - Alexopoulos, Dimitrios AU - Alexopoulos D AD - National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece. FAU - Zijlstra, Felix AU - Zijlstra F AD - Erasmus Medical Center, Rotterdam, Netherlands. FAU - Montalescot, Gilles AU - Montalescot G AD - Sorbonne University, ACTION Group, Groupe Hospitalier Pitie-Salpetriere Hospital (AP-HP), Paris, France. FAU - Angiolillo, Dominick J AU - Angiolillo DJ AD - University of Florida College of Medicine, Jacksonville, FL, USA. FAU - Krucoff, Mitchell W AU - Krucoff MW AD - Duke University Medical Center, Durham, NC, USA. FAU - Van Mieghem, Nicolas M AU - Van Mieghem NM AD - Erasmus Medical Center, Rotterdam, Netherlands. FAU - Smits, Pieter C AU - Smits PC AD - Maasstad Hospital, Rotterdam. LA - eng SI - ClinicalTrials.gov/NCT03296540 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200311 PL - United States TA - Am Heart J JT - American heart journal JID - 0370465 RN - 0 (Platelet Aggregation Inhibitors) RN - G89JQ59I13 (Prasugrel Hydrochloride) SB - IM MH - Administration, Oral MH - Aged MH - Coronary Angiography MH - Dose-Response Relationship, Drug MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Percutaneous Coronary Intervention MH - Platelet Aggregation Inhibitors/administration & dosage MH - Prasugrel Hydrochloride/*administration & dosage MH - Preoperative Period MH - ST Elevation Myocardial Infarction/diagnosis/*therapy MH - Treatment Outcome EDAT- 2020/04/10 06:00 MHDA- 2020/07/17 06:00 CRDT- 2020/04/10 06:00 PHST- 2020/01/24 00:00 [received] PHST- 2020/03/06 00:00 [accepted] PHST- 2020/04/10 06:00 [pubmed] PHST- 2020/07/17 06:00 [medline] PHST- 2020/04/10 06:00 [entrez] AID - S0002-8703(20)30079-X [pii] AID - 10.1016/j.ahj.2020.03.005 [doi] PST - ppublish SO - Am Heart J. 2020 Jun;224:10-16. doi: 10.1016/j.ahj.2020.03.005. Epub 2020 Mar 11.