Century Clot-Guided Prophylactic Rivaroxaban for Post STEMI Complicating Left Ventricular Thrombus

Study Overview
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Brief Summary
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To manage the ST-segment elevation myocardial infarction (STEMI) caused by plaque rupture, triggers platelet activation/aggregation and thrombin generation, requires dual (platelet and coagulation) pathway inhibition. However, triple antithrombotic therapy with standard dual antiplatelet therapy (DAPT) and oral anticoagulant (OAC) in the STEMI setting is a challenge, since that increase in potential risk of bleeding. Although the incidence of left ventricular thrombus (LVT) formation after STEMI decreased in modern reperfusion therapy, including primary percutaneous coronary intervention (PCI), remains at 4% to 26%, especially that complicated by anterior STEMI. The recommendation of an OAC prophylactic therapy for preventing LVT formation in current STEMI guidelines is limited. How to optimize antithrombotic therapy to balance the bleeding-thrombotic profile, and prevent LVT formation is challenging, since insufficient evidence is available from randomized trials. Century Clot analyzer is point-of-care testing that could assess the coagulate state: normal, hypo-coagulable, or hyper-coagulable states according to clot rate (CR) value. Whether Century Clot-guided rivaroxaban prophylactic therapy (2.5 mg twice daily, if the hypercoagulable state, defined as CR ≥24) in combination with standard DAPT could reduce LVT formation without increasing major bleeding is uncertain.

Detailed Description
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The Prophylactic Rivaroxaban Therapy for Post STEMI Complicating Left VENtricular Thrombus (PREVENT) study is designed to investigate the safety and efficacy of Century Clot-guided additional low-dose rivaroxaban plus DAPT as an optimal antithrombotic strategy for preventing LVT formation after anterior STEMI undergoing primary PCI. All eligible STEMI patients will be received standard DAPT (ticagrelor or clopidogrel plus aspirin). At post-PCI 12-24 hours, to be randomly assigned into Century Clot (CR)-guided rivaroxaban (2.5 mg twice daily for 1 month) in combination with DAPT and standard DAPT. Omitting rivaroxaban at post-PCI 1 month, and both groups are following a tailored-ticagrelor with dose reduction strategy (60 mg bid, or 45 mg bid if <50 kg, ≥75 yrs) or clopidogrel (75 mg qd) plus aspirin (100 mg qd) for further 11 months. The clinical outcome is the incidence of LVT formation, and net adverse clinical events (NACEs, composite of cardiac death, non-fatal myocardial infarction, TVR/TLR, stroke, and major bleeding) at post-STEMI 1 month, as well as at 12-month clinical follow-ups. In PREVENT study, the investigators hypothesize that Century Clot (CR)-guided additional rivaroxaban prophylactic therapy could reduce LVT formation without increasing bleeding after anterior STEMI, when compared with standard DAPT.

Official Title
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Safety and Efficacy of Century Clot-Guided Prophylactic Rivaroxaban Therapy for Post ST-Segment Elevation Myocardial Infarction Complicating Left Ventricular Thrombus Compared With Conventional Antiplatelet Therapy

Conditions
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STEMI - ST Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: NOAC+DAPT
* Drug: DAPT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ischemic chest discomfort for at least 30 minutes, with at least 1-mm (0.1-mv) ST-segment elevation in anterior leads on a standard 12-lead electrocardiogram. Patients provide written informed consent prior to enrollment. Exclusion Criteria: Intracranial, gastrointestinal, or urogenital bleeding within 6 months Requiring OAC therapy (eg, atrial fibrillation, deep vein thrombosis, pulmonary thromboembolism); Bleeding diathesis, thrombocytopenia (platelet <100,000/mL) or hemoglobin <10 g/dL, and CRUSADE score-based high bleeding risk Hepatic dysfunction (serum liver enzyme>3 times the normal limit) Renal failure (eGFR <15 ml/min/1.73m2 or requiring dialysis) Severe chronic obstructive pulmonary disease Severe bradycardia (sick sinus syndrome or high degree atrioventricular block without pacemaker protection) Drugs interfering with CYP3A4 metabolism (to avoid interaction with ticagrelor): ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromycin Life expectancy < 1 year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Guided NOAC and DAPT<br>The first month: rivaroxaban 2.5 mg twice daily (if CR≥24) plus standard DAPT (ticagrelor 90 mg twice daily or clopidogrel 75 mg daily plus aspirin 100 mg daily). The following 11 months: lower-dose ticagrelor 60 mg twice daily (45 mg twice daily if <50 kg, ≥75 yrs) or clopidogrel (75 mg daily) plus aspirin (100 mg daily). | Drug: NOAC+DAPT<br>* Century Clot-guided rivaroxaban plus DAPT.<br>* Other names: Rivaroxaban + ticagrelor or clopidogrel + aspirin;|
| Experimental: Unguided DAPT<br>The first month: standard DAPT. The following 11 months: lower-dose ticagrelor or clopidogrel plus aspirin. | Drug: DAPT<br>* Standard DAPT for 1 month, following lower-dose ticagrelor or clopidogrel plus aspirin for 11 months.<br>* Other names: Ticagrelor or clopidogrel + aspirin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of left ventricular thrombus (LVT) formation. | Efficacy endpoint | At 1 month | 
| The incidence of clinically significant bleeding according to International Society on Thrombosis and Hemostasis (ISTH) criteria. | Safety endpoint | At 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NACE (net adverse clinical event) | The incidence of NACE, including cardiac death, non-fatal myocardial infarction, target vessel/lesion revascularization, LVT formation, systemic embolism or stroke, and major bleeding. | At 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Century Clot analyzer; Prophylactic; Rivaroxaban; LVT; STEMI