Anticoagulation Therapy in Non-device-related Intra-cardiac Thrombus (ARGONAUT)

Anticoagulant Regimens Given to Achieve Thrombus Regression and Reduce Clinical Outcomes Among Patients With Non Device-related Intra-cardiac Thrombus: a Randomized Assessment Under Direct Oral Anticoagulant and Vitamin-k Antagonist Therapy

Left ventricular thrombus is found in 10 to 25% of patients with impaired left ventricular function following ST-segment elevation myocardial infarction and up to 20% in dilated cardiomyopathy in observational studies. Likewise, the incidence of atrial thrombus among atrial fibrillation patients treated by vitamin K antagonist (VKA) is between 0.25% and 7%. Despite anticoagulant therapy, intra-cardiac thrombus remains a severe complication associated with a high risk of systemic embolism and subsequent mortality but also bleeding events related to the anticoagulation therapy. The class of non-vitamin K antagonist direct oral anticoagulant (DOA) has emerged in the last decades and has systematically surpassed VKA in the different clinical settings by providing at minimum a similar efficacy and a better safety profile. In the absence of randomized study in the specific clinical setting of intracardiac thrombus, international Guidelines recommend, on the basis of expert opinion, the use of VKA for at least 3 to 6 months in case of left ventricular thrombus and there is no specific recommendation for thrombus management from other cardiac localizations.

In comparison to VKA, the easier management and the large evidence of better safety of DOA make it an interesting anticoagulant strategy. Data for left ventricule thrombosis treatment are limited and only supported by observational cohorts. However, these recent cohorts have shown promising data in this indication reporting similar thrombus regression following DOA in comparison to VKA and similar ischemic outcomes although no head-to-head comparison would be powered.

As a consequence, the multicentric randomized ARGONAUT trial aims to confirm these results and evaluate the impact of DOA compared to VKA on thrombus regression and clinical outcomes among patients with intracardiac thrombus, regardless of the thrombus localization and any underlying heart disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure; STEMI; Intracardiac Thrombus
• Intervention / Treatment: Drug: Vitamin K antagonist; Drug: Direct oral anticoagulant

• Study Type: Interventional
• Enrollment (Estimated): 340
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France
    • CHU Angers
  • Auxerre, France, 89000
    • CH Auxerre
  • Avignon, France
    • Ch Avignon
  • Bastia, France
    • CH Bastia
  • Bordeaux, France
    • Hôpital Cardiologique du Haut Lévêque
  • Brest, France
    • CHU Brest
  • Chartres, France
    • CH Chartres
  • Clermont-Ferrand, France
    • Chu Gabriel Montpied
  • Compiègne, France
    • CH Compiègne Noyon
  • Dijon, France
    • Hôpital privé Dijon Bourgogne
  • Grenoble, France
    • Groupe Hospitalier Mutualiste
  • Lille, France
    • Chu Lille
  • Limoges, France
    • CHU Limoges
  • Lyon, France
    • Hôpital Cardiovasculaire Louis Pradel
  • Marseille, France
    • AP-HM CHU La Timone
  • Metz, France
    • CHR Metz-Thionville
  • Montpellier, France
    • Clinique du Millénaire
  • Montpellier, France
    • CHU Arnaud de Villeneuve
  • Nantes, France
    • CHU Nantes
  • Nice, France
    • CHU Nice
  • Nîmes, France
    • CHU de Nîmes
  • Paris, France
    • CHU Pitié-Salpêtrière
  • Paris, France
    • AP-HP CHU Bichat
  • Paris, France
    • AP-HP CHU Lariboisière
  • Paris, France
    • Ap-Hp Hegp
  • Paris, France
    • AP-HP Hôpital Ambroise Paré
  • Pau, France
    • CH Francois Mitterand
  • Potiers, France
    • CHU Poitiers
  • Rennes, France
    • Chu Rennes
  • Saint-Denis, France
    • Centre Cardiologique du Nord
  • Strasbourg, France
    • CHU Strasbourg
  • Toulouse, France
    • CHU Toulouse
  • Valence, France, 26000
    • Centre Hopistalier de Valence
  • Vannes, France, 56000
    • CH Bretagne Atlantique
• Reunion
  • Saint-Denis, Reunion
    • CHU La réunion NORD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient with a non-device related intra-cardiac thrombus (all localizations in the four cavities) diagnosed by echocardiography, cardiac CT-scanner or cardiac magnetic resonance imaging independently of underlying heart disease.
• Anticoagulant naïve patient for at least 3 months
• Patient affiliated to a health insurance program
• Patient that accepted not to participate in other studies involving a study medication until the one-year follow-up visit. Registries and studies not involving a study drug are allowed.
• Patient that signed the consent form

Exclusion Criteria:

• Active internal bleeding or recent (< 6 months) major bleeding event requiring surgical procedure or transfusion
• History of intracranial, intraocular, spinal bleeding or known intracranial neoplasm, arteriovenous malformation, or aneurysm
• Severe, disabling stroke (modified Rankin score of 4 to 5, inclusive) within 3 months
• Planned invasive procedure with potential for uncontrolled bleeding
• Impaired hemostasis such as known International Normalized Ratio (INR) >1.5; past or present bleeding disorder (including congenital bleeding disorders such as von Willebrand's disease or hemophilia, acquired bleeding disorders, and unexplained clinically significant bleeding disorders), thrombocytopenia (platelet count <100,000/μL)
• Severe chronic renal failure (creat. clearance<30ml/min)
• Known significant liver disease
• Device related thrombus (mechanical valve prosthesis, left atrial appendage or septal closure devices, pacemaker leads)
• Patients with mechanical valve prosthesis
• Cardiogenic shock
• Pregnancy or breast-feeding patient
• Known allergy or hypersensitivity to VKA or DOA drugs
• Inability or unwillingness to comply with study-related procedures
• Participation in another clinical research protocol with other investigational agents or devices within the previous 30 days, planned use of investigational drugs or devices, or previous enrolment in this trial (participation in a trial of routine care is authorized at the same time)
• Patient under tutorship or curatorship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Reference treatment	Drug: Vitamin K antagonist; VKA study medications (Warfarin, Fluindione and Acenocoumarol) will be prescribed and supplied in the usual setting of patient care with respect of the international guidelines and recommended dose protocols and will not be specifically supplied for the trial. Anticoagulant treatment will be prescribed for 6 months. The recommended INR target will be [2-3] and [2-2.5] for patients treated with concomitant antiplatelet therapy. Biological monitoring will be performed at discretion of physicians as usual care.
Experimental: Direct Oral Anticoagulant	Drug: Direct oral anticoagulant; DOA study medications (Apixaban, Rivaroxaban and Dabigatran) will be prescribed and supplied in the usual setting of patient care and will not be specifically supplied for the trial. The usual doses of DOA will be prescribed: dabigatran 150mg twice a day, apixaban 5mg twice a day and rivaroxaban 20mg once a day. The adjusted doses (dabigatran 110mg twice a day, apixaban 2.5mg twice a day and rivaroxaban 15mg once a day) will be prescribed according to clinical practice treatment guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net clinical benefit of DOA in comparison to VKA in patients with intra-cardiac thrombus	Composite endpoint of all-cause death, myocardial infarction, stroke, acute peripheral emboli, acute pulmonary embolism, thrombus persistence and clinically relevant bleedings (BARC 2 to 5 bleedings)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause death between groups	Any death documented during the follow-up independently of cause of death	6 months
All cause death between groups	Any death documented during the follow-up independently of cause of death	12 months
Myocardial infarction occurrence between groups	All non-fatal MI, excluding MI type 3, which will be captured separately as death	6 months
Myocardial infarction occurrence between groups	All non-fatal MI, excluding MI type 3, which will be captured separately as death	12 months
Stroke occurrence between groups	Classified as Transient ischemic attack (TIA), Ischemic Stroke, Haemorrhagic Stroke and Undetermined Stroke	6 months
Stroke occurrence between groups	Classified as Transient ischemic attack (TIA), Ischemic Stroke, Haemorrhagic Stroke and Undetermined Stroke	12 months
Acute peripheral emboli occurrence between groups	All acute artery occlusion (limb, renal or digestive artery occlusion confirmed by clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), supported by evidence of embolism from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing	6 months
Acute peripheral emboli occurrence between groups	All acute artery occlusion (limb, renal or digestive artery occlusion confirmed by clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), supported by evidence of embolism from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing	12 months
Acute pulmonary embolism occurrence between groups	Defined as partial or complete occlusion of pulmonary artery or one of its branch confirmed by consistent clinical history and supported by evidence of embolism from surgical specimens, autopsy, angiography or vascular imaging in accordance to international guidelines	6 months
Acute pulmonary embolism occurrence between groups	Defined as partial or complete occlusion of pulmonary artery or one of its branch confirmed by consistent clinical history and supported by evidence of embolism from surgical specimens, autopsy, angiography or vascular imaging in accordance to international guidelines	12 months
Thrombus persistence between groups	Defined by cardiac imaging (echocardiography, contrast echocardiography, cardiac CT scan or cardiac MRI) as an increased thrombus dimension, a stable thrombus, or a partial thrombus regression	6 months
Thrombus persistence between groups	Defined by cardiac imaging (echocardiography, contrast echocardiography, cardiac CT scan or cardiac MRI) as an increased thrombus dimension, a stable thrombus, or a partial thrombus regression	12 months
Clinically relevant bleedings between groups	International Bleeding Academic Research Consortium (BARC) types 2 to 5	6 months
Clinically relevant bleedings between groups	International Bleeding Academic Research Consortium (BARC) types 2 to 5	12 months
Systemic embolism between groups	defined by the composite of stroke, embolic myocardial infarction, peripheral artery occlusion and acute pulmonary embolism	6 months
Systemic embolism between groups	defined by the composite of stroke, embolic myocardial infarction, peripheral artery occlusion and acute pulmonary embolism	12 months
Cardiovascular death between groups	Any death due to myocardial infarction, ischemic and haemorrhagic stroke, systemic embolism, sudden death, low-output failure, fatal arrhythmia, cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other cardiovascular cause. All unobserved deaths were assumed to be cardiovascular in nature unless a non-cardiovascular cause could be clearly provided.	6 months
Cardiovascular death between groups	Any death due to myocardial infarction, ischemic and haemorrhagic stroke, systemic embolism, sudden death, low-output failure, fatal arrhythmia, cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other cardiovascular cause. All unobserved deaths were assumed to be cardiovascular in nature unless a non-cardiovascular cause could be clearly provided.	12 months
Total thrombus recurrence between groups	Recurrence of thrombus on cardiac imaging control following a total thrombus regression during the follow-up	6 months
Total thrombus recurrence between groups	Recurrence of thrombus on cardiac imaging control following a total thrombus regression during the follow-up	12 months
Major bleedings between groups	International Bleeding Academic Research Consortium (BARC) types 3 to 5	6 months
Major bleedings between groups	International Bleeding Academic Research Consortium (BARC) types 3 to 5	12 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: benoit.lattuca@chu-nimes.fr Lattuca, CHU Nimes

Publications and helpful links

General Publications

• Lattuca B, Bouziri N, Kerneis M, Portal JJ, Zhou J, Hauguel-Moreau M, Mameri A, Zeitouni M, Guedeney P, Hammoudi N, Isnard R, Pousset F, Collet JP, Vicaut E, Montalescot G, Silvain J; ACTION Study Group. Antithrombotic Therapy for Patients With Left Ventricular Mural Thrombus. J Am Coll Cardiol. 2020 Apr 14;75(14):1676-1685. doi: 10.1016/j.jacc.2020.01.057.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Actual): February 5, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: April 11, 2023
• First Submitted That Met QC Criteria: April 11, 2023
• First Posted (Actual): April 24, 2023

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: stroke; acute coronary syndrome; embolism; direct oral anticoagulant; anticoagulation therapy
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Embolism and Thrombosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Pathological Conditions, Signs and Symptoms; ST Elevation Myocardial Infarction; Stroke; Heart Failure; Embolism; Acute Coronary Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antifibrinolytic Agents; Fibrin Modulating Agents; Hemostatics; Coagulants; Micronutrients; Vitamins; N(4)-oleylcytosine arabinoside; acarboxyprothrombin
• Other Study ID Numbers: PHRC-N/2020/BL-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No