Treatment of Post-STEMI Left Ventricular Thrombus With Optimized Anticoagulant (EARLYmyo-LVT)

May 30, 2023 updated by: RenJi Hospital

Efficacy and Safety of Anticoagulant on Early Treatment of Post-STEMI Left Ventricular Thrombus: an Open, Prospective, Randomized and Multi-centers Trial.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

280

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200127
        • Recruiting
        • Ren Ji Hospital Affliated to School of Medicine, Shanghai Jiao Tong University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rivaroxaban
rivaroxaban will be added in addition to dual antiplatelet therapy
Drug: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3 months
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
Through the study, an average of 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Through study completion, an average of 3 months and 1 year
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.
Through study completion, an average of 3 months and 1 year
Time to LVT resolution
Time Frame: from LVT detected to LVT resolution
The time from LVT detected to LVT resolution
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.
within 3 months and 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

RenJi Hospital

Collaborators

Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Shanghai 6th People's Hospital
Shanghai Minhang Central Hospital
Shanghai Fengxian District Central Hospital
Shanghai Songjiang Central Hospital
Zhoushan Hospital in Zhejiang Province

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2020

Primary Completion (Actual)

March 30, 2022

Study Completion (Estimated)

December 30, 2023

Study Registration Dates

First Submitted

November 24, 2018

First Submitted That Met QC Criteria

December 2, 2018

First Posted (Actual)

December 5, 2018

Study Record Updates

Last Update Posted (Actual)

June 1, 2023

Last Update Submitted That Met QC Criteria

May 30, 2023

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Cardiology-LVT

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on ST Segment Elevation Myocardial Infarction

Clinical Trials on Rivaroxaban

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Djibouti

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe