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

NCT03232398 | Completed Phase 3

• 1 other identifier: Hadassah 0607-16
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myocardial Infarction; Left Ventricular Thrombosis; Anticoagulants and Bleeding Disorders

Outcome Measures

Primary Outcomes (1)

• Presence and dimensions of Left ventricular thrombus (LV) as assessed by 2D echocardiography

  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.

  3 months

Secondary Outcomes (3)

• Stroke or systemic embolism

  3 months

• Major bleeding

  3 months

• All cause mortality

  3 months

Study Arms (2)

Apixaban

ACTIVE COMPARATOR

Apixaban Oral Tablet \[Eliquis\]

Drug: Apixaban Oral Tablet [Eliquis]; Drug: Warfarin

Warfarin

ACTIVE COMPARATOR

Warfarin - Vitamin K antagonist

Drug: Apixaban Oral Tablet [Eliquis]; Drug: Warfarin

Interventions

Apixaban Oral Tablet [Eliquis] 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.

Also known as: Eliquis

Apixaban; Warfarin

Warfarin DRUG

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

Also known as: Coumadin

Apixaban; Warfarin

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Hadassah Medical Organization

Jerusalem, Israel

Location

Related Publications (5)

• 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.

  PMID: 16330789 BACKGROUND

• 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.

  PMID: 2913497 BACKGROUND

• 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.

  PMID: 8409034 BACKGROUND

• 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.

  PMID: 21870978 BACKGROUND

• 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.

  PMID: 15842354 BACKGROUND

MeSH Terms

Conditions

Hemostatic Disorders

Interventions

apixaban; Warfarin

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ronny Alcalai

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Cardiac Care Unit

Study Record Dates

• First Submitted: July 16, 2017
• First Posted: July 28, 2017
• Study Start: January 1, 2018
• Primary Completion: March 31, 2021
• Study Completion: May 31, 2021
• Last Updated: August 25, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)