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Apixaban Versus Warfarin in Patients With Left Ventricular (LV) Thrombus

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ClinicalTrials.gov Identifier: NCT03232398
Recruitment Status : Recruiting
First Posted : July 28, 2017
Last Update Posted : August 7, 2019
Sponsor:
Information provided by (Responsible Party):
RONNY ALCALAI, Hadassah Medical Organization

Brief Summary:

Patients with acute ST-segment elevation myocardial infarction (STEMI) have an elevated risk of stroke, most of which are cardio-embolic in origin as a result of left ventricular (LV) thrombus formation. Anterior-wall location of a MI, in particular, can lead to the complications of LV aneurysm and/or thrombus, which some estimate occurs in approximately up to one-third of individuals within the first 2 weeks following an anterior MI.

In the absence of anti coagulation, the risk of embolization in patients with a documented LV thrombus has been reported to be between 10 and 15 percent [3]. Although there are no randomized trials evaluating the efficacy of anticoagulation in patients with an LV thrombus after MI, observational studies provide substantial supporting evidence for the recommendation to anticoagulate patients with documented LV thrombus in order to reduce the risk of embolization. The observation that most events occur within the first three months from the MI forms the basis for the recommendation that anticoagulant therapy should be started early and continued for at least three to six months after myocardial infarction. Currently the practice guidelines recommend anticoagulation after MI only in certain settings such as the presence of LV thrombus or atrial fibrillation. To date there are no data on the use of novel oral anticoagulants (NOACS) for stroke prevention in the setting of LV thrombus after acute MI.

The proposed aim of this randomized open label non inferiority clinical trial is to assess whether apixaban is as effective as VKA for the treatment of LV thrombus after acute ST segment elevation MI.

Population: Patients with evidence of LV thrombus as assessed by trans-thoracic echocardiography (TTE) 3 to 7 days post admission for acute ST-elevation MI

Intervention: The patients will be randomly assigned to treatment with apixaban or s.c enoxaparin 1mg/Kg BID followed by dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months.

The study Outcomes are the presence of LV thrombus as assessed be echo, major bleeding, and stroke or systemic embolism and death from any cause.


Condition or disease Intervention/treatment Phase
Acute Myocardial Infarction Left Ventricular Thrombosis Anticoagulants and Bleeding Disorders Drug: Apixaban Oral Tablet [Eliquis] Drug: Warfarin Phase 3

Detailed Description:

Background and Study Rationale:

Patients with acute ST-segment elevation myocardial infarction (STEMI) have an elevated risk of stroke, most of which are cardio-embolic in origin as a result of left ventricular (LV) thrombus formation. The risk for stroke after myocardial infarction (MI) is estimated to be 44-fold higher within the first 30 days, and remains 2 to 3 times higher than expected during the subsequent 3 years. Anterior-wall location of a MI, in particular, can lead to the complications of LV aneurysm and/or thrombus, which some estimate occurs in approximately up to one-third of individuals within the first 2 weeks following an anterior MI [2].

In the absence of anti coagulation, the risk of embolization in patients with a documented LV thrombus has been reported to be between 10 and 15 percent. Although there are no randomized trials evaluating the efficacy of anti coagulation in patients with an LV thrombus after MI, observational studies provide substantial supporting evidence for the recommendation to anti coagulate patients with documented LV thrombus in order to reduce the risk of embolization. The observation that most events occur within the first three months from the MI forms the basis for the recommendation that anticoagulant therapy should be started early and continued for at least three to six months after myocardial infarction.

Treatment of myocardial infarction has evolved dramatically in the past 20 years, and the vast majorities of patients undergo early coronary intervention and receive dual anti platelet therapy (DAPT). As a result, anterior MI alone does not warrant anti coagulation without evidence of LV thrombus since the combination of oral anti coagulation with DAPT carries an increased risk of bleeding. Practice guidelines recommend anti coagulation after MI only in certain settings such as the presence of LV thrombus or atrial fibrillation [5].

Recently oral thrombin inhibitors and factor Xa inhibitors (terms as novel oral anticoagulants - NOACS) have been introduced for stroke prevention in patients with non-valvular atrial fibrillation [6-8]. These agents were shown to be at least as effective as Vitamin K antagonists (VKA) such as warfarin in prevention of systemic embolism, while having an improved safety profile with less risk of bleeding.

To date there are no data on the use of NOACS for stroke prevention in the setting of LV thrombus after acute MI. Consequently, the effectiveness and safety of anti coagulation therapy with these novel agents in patients with LV thrombus warrants further investigation. The devastating impact of a stroke after an MI on morbidity and mortality, and the increasing number of patients at risk because of improved post-MI survival, making the goal of prevention of post MI stroke a major public health concern. The proposed study aims to address this important clinical topic.

Objective:

To assess whether apixaban is as effective as VKA for the treatment of LV thrombus after acute ST segment elevation MI.

Design Randomized open label non inferiority clinical trial.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: The primary efficacy endpoint will be the presence of LV thrombus as assessed be echocardiography after 3 months of treatment. Echocardiography images will be reviewed for the presence of LV thrombus by two experts who will be blinded to the study drug.
Primary Purpose: Treatment
Official Title: Apixaban Versus Warfarin in Patients With Left Ventricular (LV) Thrombus
Actual Study Start Date : January 1, 2018
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : October 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Apixaban
Apixaban Oral Tablet [Eliquis]
Drug: Apixaban Oral Tablet [Eliquis]
Apixaban 5 mg BID for 3 months. Apixaban 2.5-mg BID doses will be used in a subset of patients with two or more of the following criteria: an age of at least 80 years, a body weight of no more than 60 kg, or a serum creatinine level of 1.5 mg per deciliter (133 μmol per liter) or more. Patients with advanced renal failure (CrCl between 15 ml/min and 29 mi/min) will also receive 2.5 mg BID.
Other Name: Eliquis

Drug: Warfarin
Dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months
Other Name: Coumadin

Active Comparator: Warfarin
Warfarin - Vitamin K antagonist
Drug: Apixaban Oral Tablet [Eliquis]
Apixaban 5 mg BID for 3 months. Apixaban 2.5-mg BID doses will be used in a subset of patients with two or more of the following criteria: an age of at least 80 years, a body weight of no more than 60 kg, or a serum creatinine level of 1.5 mg per deciliter (133 μmol per liter) or more. Patients with advanced renal failure (CrCl between 15 ml/min and 29 mi/min) will also receive 2.5 mg BID.
Other Name: Eliquis

Drug: Warfarin
Dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months
Other Name: Coumadin




Primary Outcome Measures :
  1. Presence and dimensions of Left ventricular thrombus (LV) as assessed by 2D echocardiography [ Time Frame: 3 months ]
    The primary efficacy endpoint will be the presence of LV thrombus as assessed be echocardiography after 3 months of treatment with oral anti coagulation. Dimensions of the LV thrombus (if still present) will be compared to the thrombus dimensions at baseline.


Secondary Outcome Measures :
  1. Stroke or systemic embolism [ Time Frame: 3 months ]
    Clinically significant stroke or systemic embolism requiring hospitalization

  2. Major bleeding [ Time Frame: 3 months ]
    Major bleeding, according to the criteria of the International Society on Thrombosis and Haemostasis (ISTH)

  3. All cause mortality [ Time Frame: 3 months ]
    Death from any cause.



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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with evidence of LV thrombus as assessed by trans-thoracic echocardiography
  • Acute MI in last 3 months prior to enrollment

Exclusion Criteria:

  • Patients with contraindications for chronic anti coagulation
  • Patients with severe renal failure (CrCl< 15 ml/min)

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): NCT03232398


Contacts
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Contact: Ronny Alcalai, MD +972508946269 ronny@hadassah.org.il
Contact: David Leibowitz, MD +97225844530 oleibo@hadassah.org.il

Locations
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Israel
Hadassah Medical Organization Recruiting
Jerusalem, Israel
Contact: Arik Tzukert, DMD       arik@hadassah.org.il   
Contact: Hadas Lamberg       lhadas@hadassah.org.il   
Sponsors and Collaborators
Hadassah Medical Organization
Investigators
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Principal Investigator: Ronny Alcalai Hadassah Medical Organization

Publications:
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Responsible Party: RONNY ALCALAI, Director, Cardiac Care Unit, Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT03232398     History of Changes
Other Study ID Numbers: Hadassah 0607-16
First Posted: July 28, 2017    Key Record Dates
Last Update Posted: August 7, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Warfarin
Myocardial Infarction
Thrombosis
Hemostatic Disorders
Blood Coagulation Disorders
Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Embolism and Thrombosis
Hematologic Diseases
Hemorrhagic Disorders
Apixaban
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action