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
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 374
- 试验地点
- 1
- 主要终点
- The incidence of clinically significant bleeding according to International Society on Thrombosis and Hemostasis (ISTH) criteria.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Guided NOAC and DAPT
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).
干预措施: NOAC+DAPT (Drug)
Unguided DAPT
The first month: standard DAPT. The following 11 months: lower-dose ticagrelor or clopidogrel plus aspirin.
干预措施: DAPT (Drug)
结局指标
主要结局
The incidence of clinically significant bleeding according to International Society on Thrombosis and Hemostasis (ISTH) criteria.
时间窗: At 1 month
Safety endpoint
The incidence of left ventricular thrombus (LVT) formation.
时间窗: At 1 month
Efficacy endpoint
次要结局
- NACE (net adverse clinical event)(At 12 months)
研究者
Cai De Jin, MD
Principal Investigator
Zunyi Medical College