Clinical trial NCT05825573: Anticoagulation Therapy in Non-device-related Intra-cardiac Thrombus
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Intracardiac Thrombus
STEMI
Heart Failure
Keywords: anticoagulation therapy
direct oral anticoagulant
stroke
acute coronary syndrome
embolism
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2023-04-24
Enrollment: 340
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Net clinical benefit of DOA in comparison to VKA in patients with intra-cardiac thrombus
timeFrame: 6 months
Secondary outcomes:
measure: All cause death between groups
timeFrame: 6 months
measure: All cause death between groups
timeFrame: 12 months
measure: Myocardial infarction occurrence between groups
timeFrame: 6 months
measure: Myocardial infarction occurrence between groups
timeFrame: 12 months
measure: Stroke occurrence between groups
timeFrame: 6 months
measure: Stroke occurrence between groups
timeFrame: 12 months
measure: Acute peripheral emboli occurrence between groups
timeFrame: 6 months
measure: Acute peripheral emboli occurrence between groups
timeFrame: 12 months
measure: Acute pulmonary embolism occurrence between groups
timeFrame: 6 months
measure: Acute pulmonary embolism occurrence between groups
timeFrame: 12 months
measure: Thrombus persistence between groups
timeFrame: 6 months
measure: Thrombus persistence between groups
timeFrame: 12 months
measure: Clinically relevant bleedings between groups
timeFrame: 6 months
measure: Clinically relevant bleedings between groups
timeFrame: 12 months
measure: Systemic embolism between groups
timeFrame: 6 months
measure: Systemic embolism between groups
timeFrame: 12 months
measure: Cardiovascular death between groups
timeFrame: 6 months
measure: Cardiovascular death between groups
timeFrame: 12 months
measure: Total thrombus recurrence between groups
timeFrame: 6 months
measure: Total thrombus recurrence between groups
timeFrame: 12 months
measure: Major bleedings between groups
timeFrame: 6 months
measure: Major bleedings between groups
timeFrame: 12 months
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Auxerre
country: France
facility: Ch Auxerre
city: Avignon
country: France
facility: Ch Avignon
city: Bastia
country: France
facility: CH Bastia
city: Bordeaux
country: France
facility: Hôpital Cardiologique du Haut Lévêque
city: Brest
country: France
facility: CHU Brest
city: Chartres
country: France
facility: CH Chartres
city: Clermont-Ferrand
country: France
facility: CHU Gabriel Montpied
city: Compiègne
country: France
facility: CH Compiègne Noyon
city: Dijon
country: France
facility: Hôpital Privé Dijon Bourgogne
city: Grenoble
country: France
facility: Groupe Hospitalier Mutualiste
city: Lille
country: France
facility: CHU Lille
city: Limoges
country: France
facility: CHU Limoges
city: Lyon
country: France
facility: Hôpital Cardiovasculaire Louis Pradel
city: Marseille
country: France
facility: AP-HM CHU La Timone
city: Metz
country: France
facility: CHR Metz-Thionville
city: Montpellier
country: France
facility: CHU Arnaud de Villeneuve
city: Montpellier
country: France
facility: Clinique du Millenaire
city: Nantes
country: France
facility: CHU Nantes
city: Nice
country: France
facility: CHU Nice
city: Nîmes
country: France
facility: CHU de Nimes
city: Paris
country: France
facility: AP-HP CHU Bichat
city: Paris
country: France
facility: AP-HP CHU Lariboisière
city: Paris
country: France
facility: Ap-Hp Hegp
city: Paris
country: France
facility: AP-HP Hopital Ambroise Paré
city: Paris
country: France
facility: CHU Pitié-Salpêtrière
city: Pau
country: France
facility: CH Francois Mitterand
city: Potiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: CHU Rennes
city: Saint-Denis
country: France
facility: Centre Cardiologique du Nord
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Toulouse
country: France
facility: CHU Toulouse
city: Valence
country: France
facility: Centre Hopistalier de Valence
city: Vannes
country: France
facility: Ch Bretagne Atlantique
city: Saint-Denis
country: Réunion
facility: CHU La réunion NORD
Study officials:
affiliation: CHU Nimes
name: benoit.lattuca@chu-nimes.fr Lattuca
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.