CRUSHed vs. Uncrushed Prasugrel in STEMI Patients Undergoing PCI

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Cardiovascular Diseases

Intervention / Treatment
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* Drug: Prasugrel (Crushed tablets)
* Drug: Prasugrel (Integral tablets)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Crushed versus uncrushed tablets Prasugrel loading dose
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Uncrushed<br>6 Integral tablets Prasugrel as loading dose | Drug: Prasugrel (Integral tablets)<br>* loading dose of 6 integral tablets of 10mg Prasugrel<br>* Other names: 6 Integral tablets of Prasugrel 10mg;|
| Experimental: Crushed<br>6 Crushed tablets Prasugrel as loading dose | Drug: Prasugrel (Crushed tablets)<br>* loading dose of 6 crushed tablets 10mg Prasugrel<br>* Other names: 6 Crushed tablets of Prasugrel 10mg;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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STEMI