CRUSHed vs. Uncrushed Prasugrel in STEMI Patients Undergoing PCI (CompareCrush)

COMPARison of Pre-hospital CRUSHed vs. Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions

The studys evaluates the effect of prehospital administration of crushed tablets of Prasugrel loading dose (in addition to ASA and standard care) versus uncrushed tablets of Prasugrel loading dose on efficacy and safety as well as pharmacodynamics as measured by platelet reactivity using VerifyNow.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases
• Intervention / Treatment: Drug: Prasugrel (Integral tablets); Drug: Prasugrel (Crushed tablets)

Detailed Description

The study is a two-centre, randomized, 1:1 trial comparing prehospital prasugrel initiation therapy between crushed vs. uncrushed prasugrel tablets on efficacy and safety as well as pharmacodynamics in STEMI patients.

Patients with STEMI planned for primary PCI will be screened and, if inclusion criteria are met, included at first medical contact (paramedics). After enrolment, patients will be randomly assigned (1:1) to receive 60mg prasugrel loading dose by ingesting integral or crushed tablets.

The follow-up duration is 12 months, i.e. clinical outcomes will be analysed in-hospital, at 30 days, and 12 months

• Study Type: Interventional
• Enrollment (Actual): 729
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus Medical Center
  • Rotterdam, Netherlands, 3079 DZ
    • Maasstadziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Consecutive patients with STEMI planned for primary PCI:

• Deferred written informed consent within 4 hours after prasugrel loading dose
• Adult men and women aged at least 18 years
• Symptoms of acute MI of more than 30 min but less than 6 hours
• New persistent ST-segment elevation ≥ 1 mm in two or more contiguous ECG leads

Exclusion Criteria:

• Contraindication to prasugrel (e.g., hypersensitivity, active bleeding, history of previous intracranial bleed, history of any CVA including TIA, moderate to severe hepatic impairment, GI bleed within the past 6 months, major surgery within past 4 weeks)
• Patient who has received loading dose of clopidogrel or ticagrelor for the index event or are on chronic treatment of ticagrelor, or prasugrel. However, patients on maintenance dose clopidogrel for at least 7 days are included in the study (see appendix A).
• Oral anticoagulation therapy that cannot be stopped (i.e. patients requiring chronic therapy)
• Planned fibrinolytic treatment
• Patient requiring dialysis
• Known, clinically important thrombocytopenia
• Known clinically important anaemia
• Known pregnancy or lactation
• Need for a concomitant systemic therapy with strong inhibitors or strong inducers of CYP3A
• Condition which may either put the patient at risk or influence the result of the study (e.g., cardiogenic shock with severe hemodynamic instability, active cancer, risk for non-compliance, risk for being lost to follow up)
• Patient unable to swallow oral medication (i.e. intubated patients)
• Patient who have not received prasugrel loading dose in the ambulance
• Patient who vomited after randomization / receiving the loading dose prasugrel

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Uncrushed; 6 Integral tablets Prasugrel as loading dose	Drug: Prasugrel (Integral tablets); loading dose of 6 integral tablets of 10mg Prasugrel; Other Names: 6 Integral tablets of Prasugrel 10mg
Experimental: Crushed; 6 Crushed tablets Prasugrel as loading dose	Drug: Prasugrel (Crushed tablets); loading dose of 6 crushed tablets 10mg Prasugrel; Other Names: 6 Crushed tablets of Prasugrel 10mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Co-primary endpoint is the percentage of patients reaching TIMI flow grade 3 of MI culprit vessel at initial angiography or a ≥70% ST-segment resolution directly post-PCI	To assess the efficacy of crushed vs. integral tablets of prasugrel loading dose treatment by comparing the percentage of patients reaching the co-primary endpoint of TIMI flow grade 3 of MI culprit vessel at initial angiography or a ≥70% ST-segment elevation resolution directly post-PCI.	directly post PCI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of death, MI, stroke, urgent revascularization and acute stent thrombosis in hospital, at 30 days and 12 months	Percentage of patients in the following: composite of death, MI, stroke, urgent revascularization and acute stent thrombosis during inhospital stay, 30 days and 12 months of study	upto 72 hours after randomisation, at 30 days and 12 months.
Composite of death, MI, urgent revascularization during inhospital, at 30 days and 12 months of study	Percentage of patients in the following: composite of death, MI, or urgent revascularization during inhospital, 30 days and 12 months of study	30 days and 12 months
Individual endpoints during inhospital, at 30 days and 12 months of study	Percentage of patients presenting with any of the individual endpoints during inhospital, 30 days and 12 months of study	upto 72 hours after randomisation, at 30 days and 12 months.
Thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI	Percentage of patients receiving thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI	directly post PCI
Complete (≥ 70%) ST-segment elevation resolution pre-PCI and 60 min post-PCI	Complete (≥ 70%) ST-segment elevation resolution pre-PCI and 60 min post-PCI	pre-PCI and 60 min post-PCI
Corrected TIMI frame count (cTFC) at angiography, pre and post PCI.	Corrected TIMI frame count (cTFC) at angiography, pre and post PCI	pre PCI, directly post PCI
TIMI myocardial perfusion grade (TMPG) at angiography, pre and post PCI.	TIMI myocardial perfusion grade (TMPG) at angiography, pre and post PCI.	pre PCI, directly post PCI
Time-relationship (from symptom onset to 1st dose intake) on each co-primary	Time from symptom onset to 1st dose intake correlated to TIMI flow grade 3 of MI culprit vessel at initial angiography and on ≥70% ST-segment elevation resolution directly post-PCI	directly post-PCI
Time-relationship (from 1st dose intake to ECG/ angiography) on each co-primary	Time from first dose intake to ECG correlated to ≥70% ST-segment elevation resolution directly post-PCI and time from randomization to initial angiography correlated to TIMI flow grade 3 of MI culprit vessel	directly post-PCI
TIMI flow grade 3 at end of procedure.	TIMI flow grade 3 at end of procedure.	directly post PCI
Myocardial Blush at the start and end of the procedure	Myocardial Blush at the start and end of the procedure	pre PCI, directly post PCI
Maximum CK, and CK-MB levels	Maximum CK, and CK-MB levels	upto 72 hours after randomisation
Level of platelet inhibition at first medical contact, beginning and end of PCI procedure, as well as at 4 hours after prasugrel administration	Level of platelet inhibition at first medical contact, beginning and end of PCI procedure, as well as at 4 hours after prasugrel administration	at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration
Platelet reactivity, at each time point as well as over time	PRU measurements at first medical contact, beginning and end of PCI, as well as 4hours after drug administration	at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration
Rates of HPR	Percentage of patients with PRU values over HPR threshold	upto 72 hours after randomisation
Exploratory analyses within each group to evaluate any differences in PD among patients receiving morphine	PD of each group among patients stratified for morphine treatment	upto 72 hours after randomisation

Collaborators and Investigators

• Sponsor: Maasstad Hospital
• Collaborators: Daiichi Sankyo, Inc.; MicroPort Orthopedics Inc.; Research Maatschap Cardiologen Rotterdam Zuid
• Investigators: Principal Investigator: George Vlachojannis, MD, PhD, Maasstadziekenhuis; Study Director: Pieter C Smits, MD, PhD, Maasstadziekenhuis; Study Chair: Nicolas van Mieghem, MD, PhD, Erasmus Medical Center

Publications and helpful links

General Publications

• Vlachojannis GJ, Wilschut JM, Vogel RF, Lemmert ME, Delewi R, Diletti R, van der Waarden NWPL, Nuis RJ, Paradies V, Alexopoulos D, Zijlstra F, Montalescot G, Angiolillo DJ, Krucoff MW, Van Mieghem NM, Smits PC. Effect of Prehospital Crushed Prasugrel Tablets in Patients With ST-Segment-Elevation Myocardial Infarction Planned for Primary Percutaneous Coronary Intervention: The Randomized COMPARE CRUSH Trial. Circulation. 2020 Dec 15;142(24):2316-2328. doi: 10.1161/CIRCULATIONAHA.120.051532. Epub 2020 Oct 14.
• Vlachojannis GJ, Vogel RF, Wilschut JM, Lemmert ME, Delewi R, Diletti R, van Vliet R, van der Waarden N, Nuis RJ, Paradies V, Alexopoulos D, Zijlstra F, Montalescot G, Angiolillo DJ, Krucoff MW, Van Mieghem NM, Smits PC. 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. Am Heart J. 2020 Jun;224:10-16. doi: 10.1016/j.ahj.2020.03.005. Epub 2020 Mar 11.

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2017
• Primary Completion (Actual): May 1, 2021
• Study Completion (Actual): May 1, 2021

Study Registration Dates

• First Submitted: September 6, 2017
• First Submitted That Met QC Criteria: September 25, 2017
• First Posted (Actual): September 28, 2017

Study Record Updates

• Last Update Posted (Actual): May 7, 2021
• Last Update Submitted That Met QC Criteria: May 6, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: STEMI
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride
• Other Study ID Numbers: 2017-40

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No