Clinical trial NCT03296540: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiovascular Diseases
Keywords: STEMI
Lead sponsor: Maasstad Hospital
Sponsor class: OTHER
Collaborators: name: MicroPort Orthopedics Inc.
name: Daiichi Sankyo
name: Research Maatschap Cardiologen Rotterdam Zuid
First posted: 2017-09-28
Enrollment: 729
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Crushed versus uncrushed tablets Prasugrel loading dose
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: 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
timeFrame: directly post PCI
Secondary outcomes:
measure: Composite of death, MI, stroke, urgent revascularization and acute stent thrombosis in hospital, at 30 days and 12 months
timeFrame: upto 72 hours after randomisation, at 30 days and 12 months.
measure: Composite of death, MI, urgent revascularization during inhospital, at 30 days and 12 months of study
timeFrame: 30 days and 12 months
measure: Individual endpoints during inhospital, at 30 days and 12 months of study
timeFrame: upto 72 hours after randomisation, at 30 days and 12 months.
measure: Thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI
timeFrame: directly post PCI
measure: Complete (≥ 70%) ST-segment elevation resolution pre-PCI and 60 min post-PCI
timeFrame: pre-PCI and 60 min post-PCI
measure: Corrected TIMI frame count (cTFC) at angiography, pre and post PCI.
timeFrame: pre PCI, directly post PCI
measure: TIMI myocardial perfusion grade (TMPG) at angiography, pre and post PCI.
timeFrame: pre PCI, directly post PCI
measure: Time-relationship (from symptom onset to 1st dose intake) on each co-primary
timeFrame: directly post-PCI
measure: Time-relationship (from 1st dose intake to ECG/ angiography) on each co-primary
timeFrame: directly post-PCI
measure: TIMI flow grade 3 at end of procedure.
timeFrame: directly post PCI
measure: Myocardial Blush at the start and end of the procedure
timeFrame: pre PCI, directly post PCI
measure: Maximum CK, and CK-MB levels
timeFrame: upto 72 hours after randomisation
measure: Level of platelet inhibition at first medical contact, beginning and end of PCI procedure, as well as at 4 hours after prasugrel administration
timeFrame: at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration
measure: Platelet reactivity, at each time point as well as over time
timeFrame: at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration
measure: Rates of HPR
timeFrame: upto 72 hours after randomisation
measure: Exploratory analyses within each group to evaluate any differences in PD among patients receiving morphine
timeFrame: upto 72 hours after randomisation
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Rotterdam
country: Netherlands
facility: Maasstadziekenhuis
Study officials:
affiliation: Maasstadziekenhuis
name: George Vlachojannis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maasstadziekenhuis
name: Pieter C Smits, MD, PhD
role: STUDY_DIRECTOR
affiliation: Erasmus Medical Center
name: Nicolas van Mieghem, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.