Ticagrelor for PCI Post Thrombolysis

Study Overview
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Brief Summary
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Ticagrelor is a first line therapy along with aspirin for patients undergoing primary PCI for STEMI. However, many patients are still treated with fibrinolytic therapy and the safety and efficacy of Ticagrelor has not been investigated in this patients population. The present study is proposed to study the safety and efficacy of Ticagrelor in patients undergoing PCI post fibrinolytic therapy for STEMI.

Detailed Description
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The newer antiplatelet agents such as Ticagrelor have demonstrated superiority to Clopidogrel in patients presenting with acute coronary syndrome (ACS). At present Ticagrelor remains a first line therapy as an adjunct to aspirin for patients undergoing primary PCI for STEMI for reducing major adverse events. However, the safety and efficacy of Ticagrelor has not been investigated in patients with STEMI post fibrinolysis. Ticagrelor results in significantly higher platelet inhibition than aspirin or clopidogrel and may expose patients to an increased risk of bleeding if administered post thrombolysis. However, fibrinolytic therapy itself results in a prothrombotic milieu with greater activation of platelets, a condition that can be balanced with addition of stronger antiplatelet agents. Similar concerns were initially reflected for clopidogrel as an adjunct to fibrinolytic therapy but were later proven to be unsubstantiated. In fact, adjunct administration of clopidogrel to fibrinolytic therapy reduces major adverse events as shown by multiple studies and has become the standard of care recommended by guidelines. The present study is proposed to study the safety and efficacy of Ticagrelor in patients undergoing PCI post fibrinolytic therapy for STEMI.

Official Title
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The Safety and Efficacy of Ticagrelor for Coronary Stenting Post Thrombolysis (SETFAST) Trial.

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years and over. Planned PCI between 4-24 hours after administration of fibrinolytic therapy for STEMI. Treatment with aspirin and clopidogrel as an adjunct to fibrinolytic therapy. Informed written consent. Exclusion Criteria: Atrial fibrillation or need for systemic anticoagulation therapy. Prior PCI or coronary artery bypass grafting during past 3 months. Active bleeding or high risk of bleeding based upon clinical assessment. Known severe liver or renal disease or patient requiring dialysis. Concomitant oral or IV therapy with strong cytochrome (CYP3A) inhibitors which cannot be stopped. Contraindication to ticagrelor or clopidogrel. Planned surgery during the study period. Any of the following in the absence of a functioning implanted pacemaker: sick sinus syndrome, 2nd or 3rd degree AVB, documented syncope of suspected bradycardic origin. Known clinically important thrombocytopenia or anemia. Known pregnancy or lactation. Condition which may either put the patient at risk or influence the result of the study. Previous randomization in this SETFAST study. Participation in another clinical study with an investigational product or device study over the past 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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: Clopidogrel arm<br>Clopidogrel 300 mg before PCI followed by 75 mg po OD | Drug: Clopidogrel<br>* 300 mg bolus followed by 75 mg OD<br>* Other names: Plavix;|
| Experimental: Ticagrelor arm<br>Ticagrelor 180 mg before PCI followed by 90 mg po BID | Drug: Ticagrelor<br>* 180 mg bolus followed by 90 mg BID<br>* Other names: Brilinta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic platelet inhibition | Therapeutic platelet inhibition as determined by VerifyNow assay (PRU value <208) at 4±1 hours post PCI | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic platelet inhibition | Therapeutic platelet inhibition (PRU value <208) at 24±4 hours post PCI. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fibrinolytic therapy, stenting, platelet activity