Apixaban Versus Warfarin in Patients With Left Ventricular (LV) Thrombus
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| ClinicalTrials.gov Identifier: NCT03232398 |
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Recruitment Status :
Recruiting
First Posted : July 28, 2017
Last Update Posted : August 7, 2019
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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 |
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.
| 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 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Apixaban
Apixaban Oral Tablet [Eliquis]
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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 |
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Active Comparator: Warfarin
Warfarin - Vitamin K antagonist
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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 |
- 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.
- Stroke or systemic embolism [ Time Frame: 3 months ]Clinically significant stroke or systemic embolism requiring hospitalization
- Major bleeding [ Time Frame: 3 months ]Major bleeding, according to the criteria of the International Society on Thrombosis and Haemostasis (ISTH)
- 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 |
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)
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
| Contact: Ronny Alcalai, MD | +972508946269 | ronny@hadassah.org.il | |
| Contact: David Leibowitz, MD | +97225844530 | oleibo@hadassah.org.il |
| Israel | |
| Hadassah Medical Organization | Recruiting |
| Jerusalem, Israel | |
| Contact: Arik Tzukert, DMD arik@hadassah.org.il | |
| Contact: Hadas Lamberg lhadas@hadassah.org.il | |
| Principal Investigator: | Ronny Alcalai | Hadassah Medical Organization |
Publications:
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 Warfarin Apixaban Anticoagulants Factor Xa Inhibitors Antithrombins Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |