Treatment of Post-STEMI Left Ventricular Thrombus With Optimized Anticoagulant (EARLYmyo-LVT)
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|ClinicalTrials.gov Identifier: NCT03764241|
Recruitment Status : Not yet recruiting
First Posted : December 5, 2018
Last Update Posted : December 12, 2019
|Condition or disease||Intervention/treatment||Phase|
|ST Segment Elevation Myocardial Infarction Left Ventricular Thrombus||Drug: Rivaroxaban Drug: Vitamin K Antagonist||Phase 3|
Despite the fast development and popularization of reperfusion as well as adjunctive medical therapy, complications of STEMI remain critical causes of adverse events. Among them, the formation of the left ventricular thrombus (LVT) subsequent to STEMI is not rare. The incidence of STEMI-related LVT could be as higher as 31%-56% in the earlier time when thrombolysis was the mainstream of reperfusion . The risk lowers in the ear of the primary PCI, but LVT can still be detected in around 15% patients. Anterior MI is the most critical determinant of LVT. In a study including 2911 patients, 93.2% LVT occurred due to the occlusion of left artery descending (LAD). More than 2/3 of LVT was reported within the first two weeks of STEMI, late thrombus can be found in three months or even later. The existence of LVT is clearly related to increased risk of embolic events and death. In a meta-analysis in 2019, STEMI patients with LVT demonstrated a 3.97 times higher risk of embolic events than those without LVT. In a recent study, the rate of 5-year embolism in STEMI patients with LVT was up to 16.9% if without effective therapy, significantly higher than the rate of 2.9% in patients without LVT and 3% in patients with LVT but undergoing ideal therapy.
Current therapeutic guidelines recommend anticoagulant therapy for post-STEMI LVT. Since most of the LVT would be found in the acute phase of STEMI, the anticoagulant therapy is usually in addition to antiplatelet treatment. So far, Vitamin K antagonist (VKA) is still the standard medication in the treatment of LVT. The 2013 ACC/AHA guideline for STEMI management recommended adding VKA to the dual-antiplatelet regiment in patients with LVT for at least 3 months. Similarly, the 2014 ASA guideline for primary prevention of stroke gave an IIa level recommendation to use VKA adjunctive to antiplatelet medications in STEMI patients developing LVT. The treatment of VKA seems effective to both resolve LVT and decrease embolic events. In two small studies, the triple antithrombotic regimen comprising of VKA and dual antiplatelet (aspirin and clopidogrel) for 3 months resolved 88% and 92.3% LVT on echo, respectively. The addition of VKA remarkably could reduce the embolic events to 0-3% as reported in different studies.
However, the complicated titrations and the need to frequently monitor international normalized ratios (INRs) make the use of warfarin inconvenient, especially for patients who have difficulty to access medical services regularly. Therefore, the use of novel oral anticoagulants (NOACs) as a substitute for warfarin is highly attractive. However, the efficacy of NOACs in the treatment of STEMI-related LVT is not clear. Current experiences come from small series of case reports. Rivaroxaban is a potent Xa factor inhibitor. In the field of cardiology, it has become a preferred replacement of VKA in the prevention of embolic events due to the left atrial thrombus. In the X-TRA study, 15mg/QD rivaroxaban resolved 41% of left atrial thrombus. In the case of post-STEMI LVT, 15mg/QD rivaroxaban additional to dual antiplatelet therapy resolved all 4 cases of LVT in 2-4 weeks in a Cyprus study. In an American case series, 20mg /QD rivaroxaban plus one antiplatelet medication (clopidogrel) also successfully resolved LVT in 2 patients. Therefore, using NOACs to treat post-STEMI LVT is promising. The 2017 ESC guideline for STEMI management doesn't limit the choice of anticoagulation for LVT only to VKA, but the application of NOACs still needs further confirmation.
This study aims to evaluate the therapeutic efficacy and safety of rivaroxaban on the treatment of post-STEMI LVT.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||280 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Efficacy and Safety of Anticoagulant on Early Treatment of Post-STEMI Left Ventricular Thrombus: an Open, Prospective, Randomized and Multi-centers Trial.|
|Estimated Study Start Date :||February 1, 2020|
|Estimated Primary Completion Date :||March 30, 2022|
|Estimated Study Completion Date :||December 30, 2022|
rivaroxaban will be added in addition to dual antiplatelet therapy
Rivaroxaban 15mg/QD will be applied for 3 months unless severe safety outcome occurs. All patients in both group will take aspirin 100mg/QD, clopidogrel 75mg/QD and proton pump inhibitor during the intervention.
Active Comparator: Vitamin K Antagonist
warfarin will be added in addition to dual antiplatelet therapy
Drug: Vitamin K Antagonist
warfarin (INR 2.0-2.5) will be applied for 3 months unless severe safety outcome occur. All patients in both group will take aspirin 100mg/QD, clopidogrel 75mg/QD and proton pump inhibitor during the intervention.
- Rate of LVT resolution after triple antithrombotic therapy for 3 month [ Time Frame: 3 months ]The LVT resolve will be determined monthly by follow-up imaging examination (CMR or TTE). The percentage of LVT resolve at 3 months will be calculated for each group.
- Major bleeding events (ISTH criteria) through the study, an average of 12 weeks [ Time Frame: Through the study, an average of 12 weeks ]Major Bleeding events will be classified by the ISTH criteria.It is defined as clinically over bleeding that is associated with: 1. A fall in hemoglobin of 2g/dL or more or 2.A transfusion of 2 or more units of packed red blood cells or whole blood, or 3.A critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retropertioneal, or 4. A fatal outcome. All bleeding events will be documented through the study, an average of 12weeks
- Composite major adverse events through the study, an average of 3 months and 1 year [ Time Frame: Through study completion, an average of 3 months and 1 year ]The incidence of a composite adverse events, including all-cause death, recurrent myocardial infarction, ischemic stroke and other systemic embolism through 3 months and 1 year will be calculated for each group.
- Non-major bleeding events (ISTH criteria) through the study, an average of 3 months and 1 year [ Time Frame: Through study completion, an average of 3 months and 1 year ]Non-major bleeding events is identified by ISTH ctiteria.
- Time to LVT resolution [ Time Frame: from LVT detected to LVT resolution ]The time from LVT detected to LVT resolution
- Incidence of any systemic embolic events within 3 months and 1 year [ Time Frame: within 3 months and 1 year ]Incidence of any systemic embolic events within 3 months and 1 year after triple therapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03764241
|Contact: Jun Pu, Professoremail@example.com|
|Contact: Heng Ge, M.D.||firstname.lastname@example.org|
|Ren Ji Hospital Affliated to School of Medicine, Shanghai Jiao Tong University|
|Shanghai, Shanghai, China, 200127|
|Contact: Jun Pu, Professor 86-21-68383477 email@example.com|