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

Tracking Information

• First Submitted Date: September 6, 2017
• First Posted Date: September 28, 2017
• Last Update Posted Date: May 7, 2021
• Actual Study Start Date: November 28, 2017
• Actual Primary Completion Date: May 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 25, 2017)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 25, 2017)

• 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
• 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
• 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
• 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
• 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
• 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
• 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.
• 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
• 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
• TIMI flow grade 3 at end of procedure. [ Time Frame: directly post PCI ]
  TIMI flow grade 3 at end of procedure.
• 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
• Maximum CK, and CK-MB levels [ Time Frame: upto 72 hours after randomisation ]
  Maximum CK, and CK-MB levels
• 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
• 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
• Rates of HPR [ Time Frame: upto 72 hours after randomisation ]
  Percentage of patients with PRU values over HPR threshold
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CRUSHed vs. Uncrushed Prasugrel in STEMI Patients Undergoing PCI
• Official Title: COMPARison of Pre-hospital CRUSHed vs. Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions
• 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.

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
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Crushed versus uncrushed tablets Prasugrel loading dose

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Cardiovascular Diseases

Intervention

• Drug: Prasugrel (Crushed tablets)
  loading dose of 6 crushed tablets 10mg Prasugrel
  Other Name: 6 Crushed tablets of Prasugrel 10mg
• Drug: Prasugrel (Integral tablets)
  loading dose of 6 integral tablets of 10mg Prasugrel
  Other Name: 6 Integral tablets of Prasugrel 10mg

Study Arms

• Active Comparator: Uncrushed
  6 Integral tablets Prasugrel as loading dose
  Intervention: Drug: Prasugrel (Integral tablets)
• Experimental: Crushed
  6 Crushed tablets Prasugrel as loading dose
  Intervention: Drug: Prasugrel (Crushed tablets)

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 14, 2020): 729
• Original Estimated Enrollment (submitted: September 25, 2017): 674
• Actual Study Completion Date: May 1, 2021
• Actual Primary Completion Date: May 1, 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT03296540
• Other Study ID Numbers: 2017-40
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Maasstad Hospital
• Study Sponsor: Maasstad Hospital

Collaborators

• 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

• PRS Account: Maasstad Hospital
• Verification Date: May 2021