Cardiovascular Diseases
Conditions
Keywords
STEMI
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
Interventions
DRUGPrasugrel (Crushed tablets)
loading dose of 6 crushed tablets 10mg Prasugrel
DRUGPrasugrel (Integral tablets)
loading dose of 6 integral tablets of 10mg Prasugrel
Sponsors
MicroPort Orthopedics Inc.
Daiichi Sankyo
Research Maatschap Cardiologen Rotterdam Zuid
Maasstad Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Crushed versus uncrushed tablets Prasugrel loading dose
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Composite of death, MI, stroke, urgent revascularization and acute stent thrombosis in hospital, at 30 days and 12 months | 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 |
| Individual endpoints during inhospital, at 30 days and 12 months of study | 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 | 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 | 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. | 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. | 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 | 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 |
| Composite of death, MI, urgent revascularization during inhospital, at 30 days and 12 months of study | 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 |
| TIMI flow grade 3 at end of procedure. | directly post PCI | TIMI flow grade 3 at end of procedure. |
| Myocardial Blush at the start and end of the procedure | pre PCI, directly post PCI | Myocardial Blush at the start and end of the procedure |
| Maximum CK, and CK-MB levels | 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 | 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 | 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 | 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 | upto 72 hours after randomisation | PD of each group among patients stratified for morphine treatment |
| Time-relationship (from 1st dose intake to ECG/ angiography) on each co-primary | 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 |
Countries
Netherlands
Outcome results
None listed