Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis

Study Overview
=================
Brief Summary
-----------------
Administration of Ticagrelor in patients with ST elevation myocardial infarction treated with pharmacological thrombolysis

Detailed Description
-----------------
Phase III, Randomized, International, Multicenter, Open label, with Blinded Adjudication of Outcomes, Non-Inferiority Clinical Trial to Explore the Safety and Efficacy of Ticagrelor Compared with Clopidogrel in Patients with Acute Coronary Syndrome with ST Elevation Treated with Pharmacological Thrombolysis.

Official Title
-----------------
Phase III, Randomized, International, Multicenter, Open Label, With Blinded Adjudication of Outcomes, Non-Inferiority Clinical Trial to Explore the Safety and Efficacy of Ticagrelor Compared With Clopidogrel in Patients With Acute Coronary Syndrome With ST Elevation Treated With Pharmacological Thrombolysis.

Conditions
-----------------
Acute ST Segment Elevation Myocardial Infarction, Thrombolysis in Myocardial Infarction Flow

Intervention / Treatment
-----------------
* Drug: Ticagrelor 180 mg
* Drug: Clopidogrel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients of both sexes aged ≥ 18 years and < 75 years with ACS with ST segment elevation with onset during the previous 24 hours, documented by cardiac ischemic symptoms due to atherosclerosis of > 10 minutes duration at rest, treated with pharmacological thrombolysis Fibrinolytic therapy should be given to patients with STEMI and onset of ischemic symptoms within the previous 12 hours Patients with acute coronary syndrome with ST segment elevation will be included provided they present ST segment elevation at the J point in two contiguous leads in electrocardiogram with cut-points: > 0.1mV in all leads other than leads V2-V3, where the following cut points apply: > 0.2 mV in men > 40 years; > 0.25 mV in men < 40 years, or >0.15 mV in women and at least 1 of the following criteria: Angina-like chest pain or ischemic equivalent chest pain; Abnormalities above the reference value for markers of myocardial necrosis (troponin and CK-MB). The patient must be able to give informed consent in accordance with ICH GCP guidelines and local legislation and/or regulations. Exclusion Criteria: Any contraindication against the use of clopidogrel (eg, hypersensitivity, moderate or severe liver disease, active bleeding or bleeding history, history of intracranial hemorrhage) Need for oral anticoagulation therapy, Concomitant oral or IV therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, grapefruit juice N1 L/d), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or strong CYP3Ainducers (rifampin/rifampicin, phenytoin, carbamazepine) Increased risk of bradycardia events Dialysis required Known clinically important thrombocytopenia Known clinically important anemia Any other condition that may put the patient at risk or influence study results in the investigators' opinion (eg, cardiogenic shock, severe hemodynamic instability, active cancer) Participant in another investigational drug or device study within 30 d Pregnancy or lactation Any condition that increases the risk for noncompliance or being lost to follow-up Involvement in the planning or conduct of the study Previous enrollment or randomization in this study Contraindications to fibrinolytic therapy including: 15 Any prior intracranial hemorrhage Known structural cerebral vascular lesion (eg, Arterial Venous Malformation - AVM) Known malignant intracranial neoplasm (primary or metastatic) Ischemic stroke within 3 months Suspected aortic dissection Active bleeding or bleeding diathesis (excluding menses) Significant closed head trauma or facial trauma within 3 months

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ticagrelor 180 mg<br>Patients assigned to Ticagrelor will receive oral Ticagrelor, 180 mg as early as possible after the index event and not >24 h post event followed by 90 mg twice daily for 12 months. | Drug: Ticagrelor 180 mg<br>* Ticagrelor, 180 mg as early as possible after the index event and not >24 h post event followed by 90 mg twice daily for 12 months.<br>* Other names: Ticagrelor;|
| Active Comparator: Clopidogrel<br>Patients will take the 300 mg clopidogrel as early as possible after the index event and not > 24h post event, followed by 75mg/day for 12 months. For patients with > 75 years the recommended load dose is 75 mg instead 300 mg. | Drug: Clopidogrel<br>* 300 mg clopidogrel as early as possible after the index event and not > 24h post event, followed by 75mg/day for 12 months. For patients with > 75 years the recommended load dose is 75 mg instead 300 mg.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Outcome as a measure of Time to TIMI-defined first major bleeding | The primary safety endpoint is time to TIMI-defined and adjudicated first major bleeding event (including major life-threatening bleeding and other major bleeding). Bleeding TIMI Definition Major: Any intracranial hemorrhage (ICH)*, OR Clinically significant overt signs of hemorrhage associated with a drop in hemoglobin (Hgb) of ≥ 5 g/dL (or, when Hgb is not available, an absolute drop in hematocrit (Hct) of ≥ 15%). An independent blinded central adjudication committee will adjudicate all suspected primary end points. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Outcome as a measure of major cardiovascular events | Secondary efficacy combined endpoint: death from vascular causes, myocardial infarction, stroke, severe recurrent ischemia, recurrent ischemia, TIA, or other arterial thrombotic event. We will also measure the individual outcomes all-cause mortality and need for rescue PCI, as well as individual components of the combined efficacy endpoint. | 12 months | 
| Safety Outcome as a measure of bleeding event | Secondary safety endpoints: Total bleeding (major and minor) according to PLATO, TIMI and BARC definitions, minor bleeding according to the TIMI definition and major bleeding as individual endpoint according to the PLATO definition. Others safety variables will include: dyspnea, arrhythmia, bradycardia and laboratory safety tests | 12 months |