Treatment of Post-STEMI Left Ventricular Thrombus With Optimized Anticoagulant

NCT ID: NCT03764241

Last Updated: 2023-06-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-01
• Study Completion Date: 2023-12-30

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.

Conditions

ST Segment Elevation Myocardial Infarction; Left Ventricular Thrombus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rivaroxaban

rivaroxaban will be added in addition to dual antiplatelet therapy

Group Type: EXPERIMENTAL

Rivaroxaban

Intervention Type: DRUG

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.

Vitamin K Antagonist

warfarin will be added in addition to dual antiplatelet therapy

Group Type: ACTIVE_COMPARATOR

Vitamin K Antagonist

Intervention Type: DRUG

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.

Interventions

Rivaroxaban

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.

Intervention Type: 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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai 6th People's Hospital

OTHER

Sponsor Role: collaborator

Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

OTHER

Sponsor Role: collaborator

Shanghai Minhang Central Hospital

OTHER

Sponsor Role: collaborator

Shanghai Songjiang Central Hospital

UNKNOWN

Sponsor Role: collaborator

Shanghai Fengxian District Central Hospital

OTHER

Sponsor Role: collaborator

Zhoushan Hospital in Zhejiang Province

UNKNOWN

Sponsor Role: collaborator

RenJi Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Ren Ji Hospital Affliated to School of Medicine, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jun Pu, Professor

Role: CONTACT

pujun310@hotmail.com

08602168383164

Heng Ge, M.D.

Role: CONTACT

dr.geheng@foxmail.com

08602168383164

Facility Contacts

Jun Pu, Professor

Role: primary

pujun310@hotmail.com

86-21-68383477

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Other Identifiers

Cardiology-LVT

Identifier Type: -

Identifier Source: org_study_id