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CompletedNCT03296540CompareCrushUpdated May 7, 2021

CRUSHed vs. Uncrushed Prasugrel in STEMI Patients Undergoing PCI

A Phase 4 interventional study of Prasugrel (Crushed tablets) and Prasugrel (Integral tablets) in Cardiovascular Diseases, sponsored by Maasstad Hospital. Completed at 2 sites in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-05-07.

Sponsored by Maasstad Hospital · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
729
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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

02

Conditions studied

  • Cardiovascular Diseases

Keywords

  • STEMI
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
729 participants (actual)

Study arms

  • Active comparator
    Uncrushed

    6 Integral tablets Prasugrel as loading dose

    Drug: Prasugrel (Integral tablets)

  • Experimental
    Crushed

    6 Crushed tablets Prasugrel as loading dose

    Drug: Prasugrel (Crushed tablets)

Interventions

  • DrugPrasugrel (Crushed tablets)

    loading dose of 6 crushed tablets 10mg Prasugrel

    Also known as: 6 Crushed tablets of Prasugrel 10mg

  • DrugPrasugrel (Integral tablets)

    loading dose of 6 integral tablets of 10mg Prasugrel

    Also known as: 6 Integral tablets of Prasugrel 10mg

05

What researchers measure

Primary outcomes

  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

    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.

    Time frame: directly post PCI

Secondary outcomes

  1. 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

    Time frame: upto 72 hours after randomisation, at 30 days and 12 months.

  2. 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

    Time frame: 30 days and 12 months

  3. 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

    Time frame: upto 72 hours after randomisation, at 30 days and 12 months.

  4. Thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI

    Percentage of patients receiving thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI

    Time frame: directly post PCI

  5. 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

    Time frame: pre-PCI and 60 min post-PCI

  6. Corrected TIMI frame count (cTFC) at angiography, pre and post PCI.

    Corrected TIMI frame count (cTFC) at angiography, pre and post PCI

    Time frame: pre PCI, directly post PCI

  7. TIMI myocardial perfusion grade (TMPG) at angiography, pre and post PCI.

    TIMI myocardial perfusion grade (TMPG) at angiography, pre and post PCI.

    Time frame: pre PCI, directly post PCI

  8. 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

    Time frame: directly post-PCI

  9. 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

    Time frame: directly post-PCI

  10. TIMI flow grade 3 at end of procedure.

    TIMI flow grade 3 at end of procedure.

    Time frame: directly post PCI

  11. Myocardial Blush at the start and end of the procedure

    Myocardial Blush at the start and end of the procedure

    Time frame: pre PCI, directly post PCI

  12. Maximum CK, and CK-MB levels

    Maximum CK, and CK-MB levels

    Time frame: upto 72 hours after randomisation

  13. 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

    Time frame: at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration

  14. 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

    Time frame: at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration

  15. Rates of HPR

    Percentage of patients with PRU values over HPR threshold

    Time frame: upto 72 hours after randomisation

  16. 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

    Time frame: upto 72 hours after randomisation

06

Study locations

2 sites
  • Erasmus Medical Center
    Rotterdam, 3015 CE, Netherlands
  • Maasstadziekenhuis
    Rotterdam, 3079 DZ, Netherlands
07

References and documents

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. PubMed 33315489 ↗
  • 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. PubMed 32272255 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03296540
Lead sponsor
Maasstad Hospital
Collaborators
MicroPort Orthopedics Inc., Daiichi Sankyo, Research Maatschap Cardiologen Rotterdam Zuid
Responsible party
Sponsor
First posted
Sep 28, 2017
Start date
Nov 28, 2017
Primary completion
May 1, 2021
Completion
May 1, 2021
Last update
May 7, 2021

Study contacts

George Vlachojannis, MD, PhD
principal investigator · Maasstadziekenhuis
Pieter C Smits, MD, PhD
study director · Maasstadziekenhuis
Nicolas van Mieghem, MD, PhD
study chair · Erasmus Medical Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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