Clinical trial NCT03764241: Treatment of Post-STEMI Left Ventricular Thrombus With Optimized Anticoagulant
Official title: Efficacy and Safety of Anticoagulant on Early Treatment of Post-STEMI Left Ventricular Thrombus: an Open, Prospective, Randomized and Multi-centers Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: ST Segment Elevation Myocardial Infarction
Left Ventricular Thrombus
Keywords: STEMI
left ventricular thrombus
rivaroxaban
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai 6th People's Hospital
name: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
name: Shanghai Minhang Central Hospital
name: Shanghai Songjiang Central Hospital
name: Shanghai Fengxian District Central Hospital
name: Zhoushan Hospital in Zhejiang Province
First posted: 2018-12-05
Enrollment: 280
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: TREATMENT

Brief summary: Left ventricular thrombus is a common complication subsequent to ST-segment elevation myocardial infarction (STEMI) that related to increased embolic events. This study aims to assess the efficacy and safety outcomes of Rivaroxaban on the treatment of post-STEMI left ventricular thrombus.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Age:18-75 years old.
* Myocardial infarction diagnosed by 1) typical ischemic symptom, 2) elevated ST segment at the J-point in two contiguous leads (ST elevation should be ≥2mm in men ≥40years; ≥2.5mm in men \<40years, or ≥1.5mm in women regardless of age in leads V2 and V3; and ≥1mm in leads other than V2 and V3 ); 3) elevated cardiac troponin value with at least one value above 99th percentile upper reference limit（UPL); 4) confirmed by coronary angiography (CAG) or imaging evidence of new loss of anterior myocardium.
* Left ventricular thrombus (LVT) is detected by either cardiac magnetic resonance (CMR) or TTE in 45 days after symptom onset.

Exclusion Criteria:

* Any contraindication of anticoagulant therapy or unacceptable risk of bleeding

  1. Active bleeding;
  2. History of intracranial hemorrhage;
  3. Clinically significant gastrointestinal bleeding within 12 months before randomization;
  4. Severe thrombocytopenia (\<50x109/L), or Anemia (i.e. Hemoglobin \<90g/L) at screening or pre-randomization;
  5. Liver function Child-Pugh B or C
  6. Untreated arterial aneurysm, arterial or venous malformation and aorta dissection;
  7. Body weight \<40kg
* Undergoing anticoagulant therapy before STEMI onset
* Cardiovascular condition

  1. Cardiac shock
  2. Uncontrolled blood pressure (SBP\\geq180mmHg);
  3. Planned CABG within 3months
  4. Suspicious Pseudo-ventricular aneurysm
* Concomitant diseases

  1. Severe chronic or acute renal failure (CrCl\<50ml/min at screening or pre-randomization)
  2. Significantly liver disease
  3. Current substance abuse (drug or alcohol) problem
  4. Life expectancy to less than 12 months
  5. Known allergies, or intolerance to rivaroxaban
  6. Woman who is currently pregnant, or breastfeeding
  7. Other hypercoagulable state, such as malignat tumor, SLE
* Other conditions adjudicated by investigators to be unsuitable to anticoagulation

Primary outcomes:
measure: Rate of LVT resolution after triple antithrombotic therapy for 3 month
timeFrame: 3 months
measure: Major bleeding events (ISTH criteria) through the study, an average of 12 weeks
timeFrame: Through the study, an average of 12 weeks
Secondary outcomes:
measure: Composite major adverse events through the study, an average of 3 months and 1 year
timeFrame: Through study completion, an average of 3 months and 1 year
measure: Non-major bleeding events (ISTH criteria) through the study, an average of 3 months and 1 year
timeFrame: Through study completion, an average of 3 months and 1 year
measure: Time to LVT resolution
timeFrame: from LVT detected to LVT resolution
measure: Incidence of any systemic embolic events within 3 months and 1 year
timeFrame: within 3 months and 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ren Ji Hospital Affliated to School of Medicine, Shanghai Jiao Tong University
state: Shanghai
Study officials:
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