CRUSHed vs. Uncrushed Prasugrel in STEMI Patients Undergoing PCI
- Conditions
- Cardiovascular Diseases
- Interventions
- Registration Number
- NCT03296540
- Lead Sponsor
- Maasstad Hospital
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 729
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Uncrushed Prasugrel (Integral tablets) 6 Integral tablets Prasugrel as loading dose Crushed Prasugrel (Crushed tablets) 6 Crushed tablets Prasugrel as loading dose
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
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
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
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
Trial Locations
- Locations (2)
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Maasstadziekenhuis
🇳🇱Rotterdam, Netherlands