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

NCT ID: NCT03232398

Last Updated: 2021-08-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-01

Study Completion Date

2021-05-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Myocardial Infarction Left Ventricular Thrombosis Anticoagulants and Bleeding Disorders

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
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.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Apixaban

Apixaban Oral Tablet \[Eliquis\]

Group Type ACTIVE_COMPARATOR

Apixaban Oral Tablet [Eliquis]

Intervention Type DRUG

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.

Warfarin

Intervention Type DRUG

Dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months

Warfarin

Warfarin - Vitamin K antagonist

Group Type ACTIVE_COMPARATOR

Apixaban Oral Tablet [Eliquis]

Intervention Type DRUG

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.

Warfarin

Intervention Type DRUG

Dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

Warfarin

Dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Eliquis Coumadin

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Hadassah Medical Organization

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

RONNY ALCALAI

Director, Cardiac Care Unit

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Ronny Alcalai

Role: PRINCIPAL_INVESTIGATOR

Hadassah Medical Organization

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Hadassah Medical Organization

Jerusalem, , Israel

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Israel

References

Explore related publications, articles, or registry entries linked to this study.

Witt BJ, Brown RD Jr, Jacobsen SJ, Weston SA, Yawn BP, Roger VL. A community-based study of stroke incidence after myocardial infarction. Ann Intern Med. 2005 Dec 6;143(11):785-92. doi: 10.7326/0003-4819-143-11-200512060-00006.

Reference Type BACKGROUND
PMID: 16330789 (View on PubMed)

Fuster V, Halperin JL. Left ventricular thrombi and cerebral embolism. N Engl J Med. 1989 Feb 9;320(6):392-4. doi: 10.1056/NEJM198902093200610. No abstract available.

Reference Type BACKGROUND
PMID: 2913497 (View on PubMed)

Vaitkus PT, Barnathan ES. Embolic potential, prevention and management of mural thrombus complicating anterior myocardial infarction: a meta-analysis. J Am Coll Cardiol. 1993 Oct;22(4):1004-9. doi: 10.1016/0735-1097(93)90409-t.

Reference Type BACKGROUND
PMID: 8409034 (View on PubMed)

Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. doi: 10.1056/NEJMoa1107039. Epub 2011 Aug 27.

Reference Type BACKGROUND
PMID: 21870978 (View on PubMed)

Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.

Reference Type BACKGROUND
PMID: 15842354 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

Hadassah 0607-16

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Rivaroxaban in Left Ventricular Thrombus
NCT04970576 COMPLETED PHASE4
Phase III Acute Coronary Syndrome
NCT00831441 TERMINATED PHASE3
DOT HeartMate 3 Study
NCT04974684 COMPLETED NA