CRUSHed vs. Uncrushed Prasugrel in STEMI Patients Undergoing PCI

Cardiovascular Diseases Clinical Trial

— CompareCrush  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03296540
• Other study ID #: 2017-40
• Status: Completed
• Phase: Phase 4
• Start date: November 28, 2017
• Est. completion date: May 1, 2021

Study information

• Verified date: May 2021
• Source: Maasstad Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 729
• Est. completion date: May 1, 2021
• Est. primary completion date: May 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

Drug:
• Prasugrel (Crushed tablets)
loading dose of 6 crushed tablets 10mg Prasugrel
• Prasugrel (Integral tablets)
loading dose of 6 integral tablets of 10mg Prasugrel

Locations

Country	Name	City	State
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	Maasstadziekenhuis	Rotterdam

Sponsors (4)

Lead Sponsor	Collaborator
Maasstad Hospital	Daiichi Sankyo, Inc., MicroPort Orthopedics Inc., Research Maatschap Cardiologen Rotterdam Zuid

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	TIMI flow grade 3 at end of procedure.	TIMI flow grade 3 at end of procedure.	directly post PCI
Secondary	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
Secondary	Maximum CK, and CK-MB levels	Maximum CK, and CK-MB levels	upto 72 hours after randomisation
Secondary	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
Secondary	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
Secondary	Rates of HPR	Percentage of patients with PRU values over HPR threshold	upto 72 hours after randomisation
Secondary	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