Standard (180mg) Versus Double (360mg) Loading Dose of Ticagrelor in Patients With ST-elevation Myocardial Infarction (STEMI), Undergoing Primary Percutaneous Coronary Intervention (PCI)

Standard (180mg) Versus Double (360mg) Loading Dose of Ticagrelor in Patients With ST-elevation Myocardial Infarction (STEMI), Undergoing Primary Percutaneous Coronary Intervention (PCI): a Multi-center Randomized Parallel Pharmacodynamic Study.

This is a multi-center, prospective, randomized, single-blind, investigator initiated, pharmacodynamic study of parallel design, performed at 3 institutions (Patras University Hospital; Evangelismos Athens General Hospital; Gennimatas Athens General Hospital).

Patients with ST elevation myocardial infarction (symptom onset < 12 hours), undergoing primary percutaneous coronary intervention, who are antiplatelet naïve (Group A) or present high residual PR (defined as PRU ≥ 208) immediately before primary percutaneous coronary intervention, will be randomized after informed consent, in a 1:1 ratio to either:

Ticagrelor 180mg loading dose (LD), followed by a 90mg x2 maintenance dose (MD )starting 12±6 hours post LD Or Ticagrelor 360mg loading dose (LD), followed by a 90mg x2 maintenance dose (MD) starting 12±6 hours post LD Platelet reactivity assessment will be performed at randomization (Hour 0) and at 0.5, 1, 2, 4 hours after randomization, using the VerifyNow assay, in platelet reactivity units (PRU).

Documentation of major adverse cardiac events (death, myocardial infarction, stroke, urgent revascularization procedure with PCI or CABG) and bleeding (according to Bleeding Academic Research Consortium criteria) will be performed until patient's discharge.

Study Overview

• Status: Completed
• Conditions: ST-elevation Myocardial Infarction
• Intervention / Treatment: Drug: Ticagrelor; Drug: Ticagrelor

• Study Type: Interventional
• Enrollment (Actual): 83
• 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 (onset of pain < 12 hours) with indication for primary PCI
3. Antiplatelet naïve or presenting HTPR (≥ 208 PRU) immediately before primary percutaneous coronary intervention
4. Informed consent obtained in writing

Exclusion Criteria

• Pregnancy
• Breastfeeding
• Inability to give informed consent or high likelihood of being unavailable until the Day 5
• 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)
• Known hypersensitivity to ticagrelor
• History of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 3 months.
• Other bleeding diathesis, or considered by investigator to be at high risk for bleeding
• Any previous history of stroke, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm).
• Thrombocytopenia (< 100.000/μL) at randomization
• Anaemia (Hct < 30%) at randomization
• Polycytaemia (Hct > 52%) at randomization
• Periprocedural IIb/IIIa inhibitors administration
• Thrombolysis administration
• 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 impairment

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: Ticagrelor 180mg loading dose	Drug: Ticagrelor; Ticagrelor 360mg loading dose immediately pre prior percutaneous coronary intervention 360mg loading dose; Drug: Ticagrelor; Ticagrelor 180mg loading dose 180mg loading dose
Experimental: Ticagrelor 360mg loading dose	Drug: Ticagrelor; Ticagrelor 360mg loading dose immediately pre prior percutaneous coronary intervention 360mg loading dose; Drug: Ticagrelor; Ticagrelor 180mg loading dose 180mg loading dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
platelet reactivity at 1 hour post randomization in Group A, between the 2 treatment arms.	platelet reactivity at 1 hour post randomization in Group A, between the 2 treatment arms.	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. Platelet reactivity at 1 hour post randomization in Group B, between the 2 treatment arms.	1. Platelet reactivity at 1 hour post randomization in Group B, between the 2 treatment arms.	1 hour
2. Platelet reactivity at 0.5 hour post randomization between the 2 treatment arms separately for Group A and B	Platelet reactivity at 0.5 hour post randomization between the 2 treatment arms separately for Group A and B	0.5 hour
Platelet reactivity at 2 hours post randomization between the 2 treatment arms separately for Group A and B	Platelet reactivity at 2 hours post randomization between the 2 treatment arms separately for Group A and B	2 hours
Platelet reactivity at 4 hours post randomization between the 2 treatment arms separately for Group A and B	Platelet reactivity at 4 hours post randomization between the 2 treatment arms separately for Group A and B	4 hours
3. High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 0.5 hour post randomization between the 2 treatment arms, separately for Group A and B	High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 0.5 hour post randomization between the 2 treatment arms, separately for Group A and B	0.5 hour
High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 1 hour post randomization between the 2 treatment arms, separately for Group A and B	High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 1 hour post randomization between the 2 treatment arms, separately for Group A and B	1 hour
High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 2 hours post randomization between the 2 treatment arms, separately for Group A and B	High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 2 hours post randomization between the 2 treatment arms, separately for Group A and B	2 hours
High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 4 hours post randomization between the 2 treatment arms, separately for Group A and B	High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 4 hours post randomization between the 2 treatment arms, separately for Group A and B	4 hours
Occurrence of any 5-day bleeding event (BARC Types 1-5)	Occurrence of any 5-day bleeding event (BARC Types 1-5)	5 days
Occurrence of 5-day MACEs	Occurrence of 5-day MACEs	5 days

Collaborators and Investigators

• Sponsor: University of Patras
• Investigators: Principal Investigator: Dimitrios Alexopoulos, MD, University Hospital of Patras

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: April 9, 2012
• First Submitted That Met QC Criteria: April 10, 2012
• First Posted (Estimate): April 11, 2012

Study Record Updates

• Last Update Posted (Estimate): April 10, 2013
• Last Update Submitted That Met QC Criteria: April 9, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Ticagrelor; Platelet reactivity; ST elevation acute myocardial infarction
• 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
• Other Study ID Numbers: PATRASCARDIOLOGY-10