Anticoagulation Therapy in Non-device-related Intra-cardiac Thrombus

NCT ID: NCT05825573

Last Updated: 2025-08-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 340 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-15
• Study Completion Date: 2026-02-28

Brief Summary

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.

Conditions

Intracardiac Thrombus; STEMI; Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Reference treatment

Group Type: ACTIVE_COMPARATOR

Vitamin K antagonist

Intervention Type: DRUG

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.

Direct Oral Anticoagulant

Group Type: EXPERIMENTAL

Direct oral anticoagulant

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Nīmes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

benoit.lattuca@chu-nimes.fr Lattuca

Role: PRINCIPAL_INVESTIGATOR

CHU Nimes

Locations

CHU Angers

Angers, , France

Ch Auxerre

Auxerre, , France

Ch Avignon

Avignon, , France

CH Bastia

Bastia, , France

Hôpital Cardiologique du Haut Lévêque

Bordeaux, , France

CHU Brest

Brest, , France

CH Chartres

Chartres, , France

CHU Gabriel Montpied

Clermont-Ferrand, , France

CH Compiègne Noyon

Compiègne, , France

Hôpital Privé Dijon Bourgogne

Dijon, , France

Groupe Hospitalier Mutualiste

Grenoble, , France

CHU Lille

Lille, , France

CHU Limoges

Limoges, , France

Hôpital Cardiovasculaire Louis Pradel

Lyon, , France

AP-HM CHU La Timone

Marseille, , France

CHR Metz-Thionville

Metz, , France

CHU Arnaud de Villeneuve

Montpellier, , France

Clinique du Millenaire

Montpellier, , France

CHU Nantes

Nantes, , France

CHU Nice

Nice, , France

CHU de Nimes

Nîmes, , France

AP-HP CHU Bichat

Paris, , France

AP-HP CHU Lariboisière

Paris, , France

Ap-Hp Hegp

Paris, , France

AP-HP Hopital Ambroise Paré

Paris, , France

CHU Pitié-Salpêtrière

Paris, , France

CH Francois Mitterand

Pau, , France

CHU Poitiers

Potiers, , France

CHU Rennes

Rennes, , France

Centre Cardiologique du Nord

Saint-Denis, , France

CHU Strasbourg

Strasbourg, , France

CHU Toulouse

Toulouse, , France

Centre Hopistalier de Valence

Valence, , France

Ch Bretagne Atlantique

Vannes, , France

CHU La réunion NORD

Saint-Denis, , Reunion

Countries

France; Reunion

References

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.

Reference Type: BACKGROUND

PMID: 32273033 (View on PubMed)

Other Identifiers

PHRC-N/2020/BL-01

Identifier Type: -

Identifier Source: org_study_id