Ticagrelor in Comparison to Prasugrel for Early Inhibition of Platelet Reactivity in Patients With ST-elevation Myocardial Infarction (STEMI), Undergoing Primary Percutaneous Coronary Intervention (PCI)

This is a single-center, randomized, single-blind, investigator-initiated, pharmacodynamic study with a parallel design. Patients with ST elevation myocardial infarction, undergoing primary percutaneous coronary intervention will be randomized after informed consent, in a 1:1 ratio to the following treatment groups:

Group Α: Ticagrelor 180mg loading dose (LD), followed by a 90mg x2 maintenance dose (MD)starting 12±6 hours post LD, until Day 5 (5 days after randomization) Group Β: Prasugrel 60 mg LD followed by 10mg x1 MD starting 24 hours post LD, until Day 5 (5 days after randomization).

Platelet reactivity assessment will be performed at randomization (Hour 0) and at 1, 2, 6, 24 hours after randomization, 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: Platelet Reactivity
• Intervention / Treatment: Drug: Prasugrel; Drug: Ticagrelor

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Achaia
    • Rio, Achaia, Greece, 26500
      • Cardiology Department Patras University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 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. Informed consent obtained in writing

Exclusion Criteria:

• Pregnancy
• Breastfeeding
• Inability to give informed consent or high likelihood of being unavailable until the Day 5
• Prior PCI performed within 30 days prior to randomization
• Cardiogenic shock
• Major periprocedural complications (death, stent thrombosis, vessel perforation, arrhythmias requiring cardioversion, temporary pacemaker insertion or intravenous antiarrhythmic agents, respiratory failure requiring intubation, vascular injury (arteriovenous shunt, retroperitoneal bleeding), major bleeding (need for bood transfusion or drop in haemoglobin post-PCI by ≥ 5 gr/ dl or intracranial bleeding).
• Unsuccessful PCI (residual stenosis > 30% or flow < ΤΙΜΙ 3) or planned staged PCI in the next 5 days after randomization
• Requirement for oral anticoagulant prior to the Day 5 visit
• Current or planned therapy with other thienopyridine class of ADP receptor inhibitors.
• Known hypersensitivity to prasugrel or ticagrelor
• History of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 6 months.
• Other bleeding diathesis, or considered by investigator to be at high risk for bleeding.
• Any previous history of ischemic stroke, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm).
• Thombocytopenia (<100.000 / μL) at randomization
• Anaemia (Hct <30%) at randomization
• Polycytaemia (Hct > 52%) at randomization
• Periprocedural IIb/IIIa inhibitors administration
• Severe allergy to contrast agent, unfractionated heparin, enoxaparin or bivalirudin that cannot be adequately premedicated.
• Recent (< 6 weeks) major surgery or trauma, including GABG.
• 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.
• Concomitant oral or IV therapy with strong CY P3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazana vir, grapefruit juice N1 L/d), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or strong CYP3A inducers (rifampin /rifampicin, phenytoin, carbamazepine).
• Increased risk of bradycardiac events.
• Dialysis required.
• Severe uncontrolled chronic obstructive pulmonary disease
• Known severe hepatic impairement

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
Active Comparator: Prasugrel; Prasugrel 60mg LD followed by 10mg MD starting post 24 hours	Drug: Prasugrel; Prasugrel 60mg LD followed by 10mg x1 MD starting post 24 hours
Experimental: Ticagrelor; Ticagrelor 180mg LD followed by 90mg x2 MD starting post 12±6 hours	Drug: Ticagrelor; Ticagrelor 180mg LD followed by 90mg x2 MD starting after 12±6 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet reactivity	Platelet reactivity Platelet assessed by VerifyNow P2Y12 assay 1 hour post randomization	1hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet reactivity	Platelet Reactivity assessed by Multiplate analyzer assay 1 hour post randomization	1 hour
Platelet reactivity	Platelet reactivity assessed by the VerifyNow assay 2 hours post randomization	2 hours
Platelet reactivity	Platelet Reactivity assessed by Multiplate analyzer 2 hours post randomization	2 hours
Platelet reactivity	Platelet Reactivity assessed by VerifyNow P2Y12 assay 6 hours post randomization	6 hours
Platelet reactivity	Platelet Reactivity assessed by Multiplate analyzer 6 hours post randomization	6 hours
Platelet reactivity	Platelet Reactivity assessed by VerifyNow P2Y12 assay 24 hours post randomization	24 hours
Platelet reactivity	Platelet Reactivity assessed by Multiplate analyzer 24 hours post randomization	24 hours
Platelet reactivity	Platelet Reactivity assessed by VerifyNow P2Y12 assay 5 days post randomization	5 days
Platelet reactivity	Platelet Reactivity assessed by Multiplate analyzer 5 days post randomization	5 days

Collaborators and Investigators

• Sponsor: University of Patras

Publications and helpful links

General Publications

• Alexopoulos D, Xanthopoulou I, Gkizas V, Kassimis G, Theodoropoulos KC, Makris G, Koutsogiannis N, Damelou A, Tsigkas G, Davlouros P, Hahalis G. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv. 2012 Dec;5(6):797-804. doi: 10.1161/CIRCINTERVENTIONS.112.972323. Epub 2012 Nov 20.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: October 27, 2011
• First Submitted That Met QC Criteria: October 31, 2011
• First Posted (Estimate): November 1, 2011

Study Record Updates

• Last Update Posted (Estimate): April 10, 2012
• Last Update Submitted That Met QC Criteria: April 9, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Ticagrelor; Prasugrel; 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; Ticagrelor; Prasugrel Hydrochloride
• Other Study ID Numbers: PATRASCARDIOLOGY-8