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Trial record 77 of 156 for:    warfarin AND Vitamin K

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 5, 2018
Sponsor:
Information provided by (Responsible Party):
RenJi Hospital

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.

Condition or disease Intervention/treatment Phase
ST Segment Elevation Myocardial Infarction Left Ventricular Thrombus Drug: Rivaroxaban Drug: Vitamin K Antagonist Phase 3

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 1993, STEMI patients with LVT demonstrated a 5.45 times higher risk (95%CI 3.02-9.83)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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 520 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 : April 1, 2019
Estimated Primary Completion Date : March 30, 2022
Estimated Study Completion Date : December 30, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Rivaroxaban

Arm Intervention/treatment
Experimental: Rivaroxaban
rivaroxaban will be added in addition to dual antiplatelet therapy
Drug: Rivaroxaban
Rivaroxaban 15mg/QD will be applied for 12 weeks 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 12 weeks 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.




Primary Outcome Measures :
  1. The percentage of LVT resolve at 12 weeks [ Time Frame: at 12 weeks ]
    The LVT resolve will be determined monthly by follow-up imaging examination (CMR or TTE). The percentage of LVT resolve at 12 weeks will be calculated for each group.

  2. Bleeding events (ISTH criteria) through the study, an average of 12 weeks [ Time Frame: through the study, an average of 12 weeks ]
    Bleeding events will be classified by the ISTH criteria. Major bleeding is defined using ISTH criteria 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


Secondary Outcome Measures :
  1. Composite major adverse events through the study, an average of 12 weeks [ Time Frame: through study completion, an average of 12 weeks ]
    The incidence of a composite adverse events, including all-cause death, recurrent myocardial infarction, ischemic stroke and other systemic embolism through 12 weeks will be calculated for each group.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age:18-75 years old.
  • Anterior 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 the first month 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. Thrombocytopenia, unknown severe anemia at screening or pre-randomization;
    5. Arterial aneurysm, arterial or venous malformation and aorta dissection.
  • Except for subjects who are taking anti-thrombotic therapy (anticoagulation or anti-platelet) at the time of screening

    1. After heart valvular replacement;
    2. History of PCI or CABG;
    3. Subacute bacterial endocarditis;
    4. Venous thrombus, pulmonary thrombi embolism and other thrombophilia under anti-thrombotic therapy.
  • Complex heart condition

    1. Cardiac shock (persistent SBP<90 mmHg accompanies with deficient organ perfusion after fluid infusion);
    2. Has ventricular arrhythmias refractory to treatment at the time of randomization
    3. Uncontrolled blood pressure (SBP≥160mmHg);
    4. Undergone or has a CABG planned.
  • Severe complication

    1. Body weigh <40kg or >125kg;
    2. Severe chronic or acute renal failure (CrCl <30 mL/min at screening or pre-randomization);
    3. Significantly liver disease,or liver function test abnormal at screening (confirmed with repeat test): ALT >5 times the upper limit of normal or 3 times the upper limits of normal plus total bilirubin >2 times the upper limits of normal;
    4. Severe anemia (i.e. Hemoglobin<9g/dL) at screening or pre-randomization;
    5. Has a current substance abuse (drug or alcohol) problem or a history within the previous 6 months;
    6. Has any severe condition that would limit life expectancy to less than 12 months;
    7. Known allergies, hypersensitivity, or intolerance to rivaroxaban;
    8. Woman who is pregnant, breastfeeding or planning to become pregnant while enrolled in this study;
    9. Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (egg, compromise the well-being) of the subject or that could prevent, limit or confound the protocol-specified assessments.

Information from the National Library of Medicine

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


Contacts
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Contact: Jun Pu, Professor 08602168383164 pujun310@hotmail.com
Contact: Heng Ge, M.D. 08602168383164 dr.geheng@foxmail.com

Locations
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China, Shanghai
Ren Ji Hospital Affliated to School of Medicine, Shanghai Jiao Tong University Not yet recruiting
Shanghai, Shanghai, China, 200127
Contact: Jun Pu, Professor    86-21-68383477    pujun310@hotmail.com   
Sponsors and Collaborators
RenJi Hospital

Publications:

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Responsible Party: RenJi Hospital
ClinicalTrials.gov Identifier: NCT03764241     History of Changes
Other Study ID Numbers: Cardiology-LVT
First Posted: December 5, 2018    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by RenJi Hospital:
STEMI
left ventricular thrombus
rivaroxaban
Additional relevant MeSH terms:
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Vitamins
Vitamin K
Myocardial Infarction
Thrombosis
ST Elevation Myocardial Infarction
Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Embolism and Thrombosis
Rivaroxaban
Anticoagulants
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifibrinolytic Agents
Fibrin Modulating Agents
Hemostatics
Coagulants