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

University of Patras

Status and phase: Completed; Phase 4

Conditions: ST-elevation Myocardial Infarction

Treatments: Drug: Ticagrelor

Study type: Interventional

Funder types: Other

Identifiers

NCT01575795

PATRASCARDIOLOGY-10

Details and patient eligibility

About

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.

Enrollment: 83 patients

Sex: All

Ages: 18 to 95 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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83 participants in 2 patient groups

Ticagrelor 180mg loading dose

Active Comparator group

Description:

Ticagrelor 180mg loading dose

Treatment:

Drug: Ticagrelor

Drug: Ticagrelor

Ticagrelor 360mg loading dose

Experimental group

Description:

Ticagrelor 360mg loading dose

Treatment:

Drug: Ticagrelor

Drug: Ticagrelor