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

• ClinicalTrials.gov Identifier: NCT03296540
• Recruitment Status: Completed
• First Posted: September 28, 2017
• Last Update Posted: May 7, 2021
• Sponsor: Maasstad Hospital
• Collaborators: MicroPort Orthopedics Inc.; Daiichi Sankyo, Inc.; Research Maatschap Cardiologen Rotterdam Zuid
• Information provided by (Responsible Party): Maasstad Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cardiovascular Diseases	Drug: Prasugrel (Crushed tablets); Drug: Prasugrel (Integral tablets)	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 729 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Crushed versus uncrushed tablets Prasugrel loading dose
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: COMPARison of Pre-hospital CRUSHed vs. Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions
• Actual Study Start Date: November 28, 2017
• Actual Primary Completion Date: May 1, 2021
• Actual Study Completion Date: May 1, 2021

Arms and Interventions

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 Name: 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 Name: 6 Crushed tablets of Prasugrel 10mg

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: 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.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Netherlands

Erasmus Medical Center

Rotterdam, Netherlands, 3015 CE

Maasstadziekenhuis

Rotterdam, Netherlands, 3079 DZ

Sponsors and Collaborators

Maasstad Hospital

MicroPort Orthopedics Inc.

Daiichi Sankyo, 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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Maasstad Hospital
• ClinicalTrials.gov Identifier: NCT03296540
• Other Study ID Numbers: 2017-40
• First Posted: September 28, 2017
• Last Update Posted: May 7, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Maasstad Hospital:

STEMI

Additional relevant MeSH terms:

Cardiovascular Diseases; Prasugrel Hydrochloride; Platelet Aggregation Inhibitors