Clinical trial NCT06013020: Century Clot-Guided Prophylactic Rivaroxaban for Post STEMI Complicating Left Ventricular Thrombus
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: STEMI - ST Elevation Myocardial Infarction
Keywords: Century Clot analyzer; Prophylactic; Rivaroxaban; LVT; STEMI
Lead sponsor: Zunyi Medical College
Sponsor class: OTHER
First posted: 2023-08-28
Enrollment: 374
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The incidence of left ventricular thrombus (LVT) formation.
timeFrame: At 1 month
measure: The incidence of clinically significant bleeding according to International Society on Thrombosis and Hemostasis (ISTH) criteria.
timeFrame: At 1 month
Secondary outcomes:
measure: NACE (net adverse clinical event)
timeFrame: At 12 months
Other outcomes:
Locations:
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
Study officials:
affiliation: Zunyi Medical College
name: Cai De Jin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Camaj A, Fuster V, Giustino G, Bienstock SW, Sternheim D, Mehran R, Dangas GD, Kini A, Sharma SK, Halperin J, Dweck MR, Goldman ME. Left Ventricular Thrombus Following Acute Myocardial Infarction: JACC State-of-the-Art Review. J Am Coll Cardiol. 2022 Mar 15;79(10):1010-1022. doi: 10.1016/j.jacc.2022.01.011.
citation: Weitz JI, Angiolillo DJ, Geisler T, Heitmeier S. Dual Pathway Inhibition for Vascular Protection in Patients with Atherosclerotic Disease: Rationale and Review of the Evidence. Thromb Haemost. 2020 Aug;120(8):1147-1158. doi: 10.1055/s-0040-1713376. Epub 2020 Jun 28.
citation: Yang WX, Lai CL, Chen FH, Wang JR, Ji YR, Wang DX. The value of Sonoclot detection technology to guide the clinical medication of the perioperative anticoagulation and antiplatelet therapy in patients with acute myocardial infarction undergoing emergent PCI. Exp Ther Med. 2017 Jun;13(6):2917-2921. doi: 10.3892/etm.2017.4336. Epub 2017 Apr 13.