Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Reactivity in Patients With ST-elevation Myocardial Infarction (STEMI) (PRO-GR-4)

Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Reactivity in Patients With ST-elevation Myocardial Infarction (STEMI), Undergoing Primary Percutaneous Coronary Intervention (PCI)and Presenting With High Platelet Reactivity, as Assessed With a Point of Care Assay, After 600mg Clopidogrel Loading Dose

This is a single-center, randomized, single-blind, investigator-initiated, pharmacological study with a parallel design. Patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention and presenting high platelet reactivity as assessed with the Verify Now P2Y12 assay-Accumetrics(Platelet Reactivity Units -PRU≥235) at 2 hours post-clopidogrel 600mg LD (Day 0), as assessed with the Verify Now P2Y12 assay, will be randomized after informed consent, in a 1:1 ratio to the following treatment groups:

Group Α: Clopidogrel 150mg per day,starting from Day 1 until Day 5 (5 days after randomization) Group Β: Prasugrel 60 mg immediate loading (on Day 0) followed by 10mg/day starting from Day 1 until Day 5 (5 days after randomization).

Platelet reactivity assessment will be performed 2 hours after randomization (Day 0), 24 h after randomization (Day 1) and on Day 5. Documentation of major adverse cardiac events (death, myocardial infarction, stroke, revascularization procedure with PCI or CABG)and serious adverse events (bleeding, other adverse events)will be performed until Day 5.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction
• Intervention / Treatment: Drug: Prasugrel; Drug: Clopidogrel

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Phase 3

Contacts and Locations

Study Locations

• Greece
  • Patras, Greece, 26500
    • Patras University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 years old
2. Patients with STEMI undergoing primary PCI with stenting
3. Platelet reactivity in PRU ≥235 2 hours post 600 mg clopidogrel loading dose
4. Informed consent obtained in writing

Exclusion Criteria:

1. Treatment with other investigational agents (including placebo) or devices within 30 days prior to randomization or planned use of investigational agents or devices prior to the Day 5.
2. Pregnancy
3. Breastfeeding
4. Inability to give informed consent or high likelihood of being unavailable until Day 5.
5. Cardiogenic shock
6. Major periprocedural complications (death, stent thrombosis, vessel perforation, arrhythmias requiring cardioversion, temporary pacemaker insertion or intravenous antiarrhythmic agents, respiratory failure requiring intubation, vascular injury (pseudoaneurysm, arteriovenous shunt, retroperitoneal bleeding or hematoma >5 cm at the arterial catheter insertion site), major bleeding (need for bood transfusion or drop in haemoglobin post-PCI by ≥ 5 gr/ dl or intracranial bleeding).
7. Unsuccessful PCI (residual stenosis > 30% or flow < ΤΙΜΙ 3) or planned staged PCI in the next 5 days after randomization
8. Requirement for oral anticoagulant prior to the Day 5
9. Current or planned therapy with other thienopyridine class of ADP receptor inhibitors.
10. Known hypersensitivity to prasugrel or ticagrelor
11. History of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 6 months.
12. Other bleeding diathesis, or considered by investigator to be at high risk for bleeding on thienopyridine therapy.
13. Any previous history of ischemic stroke, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm).
14. Thrombocytopenia (<100.000 / μL) at randomization
15. Anaemia (Hct <30%) at randomization
16. Polycythaemia (Hct > 52%) at randomization
17. Periprocedural IIb/IIIa inhibitors administration
18. Severe allergy to contrast agent, unfractionated heparin, enoxaparin or bivalirudin that cannot be adequately premedicated.
19. Recent (< 6 weeks) major surgery or trauma, including GABG.
20. Subjects receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors that cannot be discontinued for the duration of the study.
21. INR>1.5 at randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prasugrel; Prasugrel 60mg immediate loading dose (Day 0)followed by 10mg/day starting from Day 1 until Day 5	Drug: Prasugrel; Prasugrel 60mg immediate loading dose (Day 0)followed by 10mg/day starting from Day 1 until Day 5
Active Comparator: Clopidogrel; Clopidogrel 150mg/day starting from Day 1 until Day 5	Drug: Clopidogrel; Clopidogrel 150mg/d starting from Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet reactivity	Platelet Reactivity assessed by VerifyNow P2Y12 assay 24 hours post randomization	24 hours post randomization (Day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet reactivity	Platelet Reactivity assessed by VerifyNow P2Y12 assay 2 hours post randomization	2 hours post randomization (Day 0)
Platelet reactivity	Platelet reactivity assessed by VerifyNow P2Y12 assay 5 days post randomization	5 days post randomization (Day 5)
Hyporesponsiveness rate	Hyporesponsiveness rate (PRU≥235 assessed with the VerifyNow P2Y12 assay)2 hours post randomization	2 hours post randomization (Day 0)
Hyporesponsiveness rate	Hyporesponsiveness rate (PRU≥235 assessed with the VerifyNow P2Y12 assay)24 hours post randomization	24 hours post randomization (Day 1)
Hyporesponsiveness rate	Hyporesponsiveness rate (PRU≥235 assessed with the VerifyNow P2Y12 assay)5 Days post randomization	5 days post randomization (Day 5)

Collaborators and Investigators

• Sponsor: University of Patras

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: April 15, 2011
• First Submitted That Met QC Criteria: April 19, 2011
• First Posted (Estimate): April 20, 2011

Study Record Updates

• Last Update Posted (Estimate): September 30, 2011
• Last Update Submitted That Met QC Criteria: September 29, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: prasugrel; clopidogrel; primary percutaneous coronary intervention; high platelet reactivity
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Prasugrel Hydrochloride
• Other Study ID Numbers: PATRASCARDIOLOGY-4