MedPath

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

Phase 3
Recruiting
Conditions
Intracardiac Thrombus
Heart Failure
STEMI
Interventions
Drug: Direct oral anticoagulant
Registration Number
NCT05825573
Lead Sponsor
Centre Hospitalier Universitaire de Nīmes
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
340
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Direct Oral AnticoagulantDirect oral anticoagulant-
Reference treatmentVitamin K antagonist-
Primary Outcome Measures
NameTimeMethod
Net clinical benefit of DOA in comparison to VKA in patients with intra-cardiac thrombus6 months

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)

Secondary Outcome Measures
NameTimeMethod
All cause death between groups12 months

Any death documented during the follow-up independently of cause of death

Myocardial infarction occurrence between groups12 months

All non-fatal MI, excluding MI type 3, which will be captured separately as death

Stroke occurrence between groups12 months

Classified as Transient ischemic attack (TIA), Ischemic Stroke, Haemorrhagic Stroke and Undetermined Stroke

Acute peripheral emboli occurrence between groups12 months

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

Acute pulmonary embolism occurrence between groups12 months

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

Thrombus persistence between groups12 months

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

Clinically relevant bleedings between groups12 months

International Bleeding Academic Research Consortium (BARC) types 2 to 5

Systemic embolism between groups12 months

defined by the composite of stroke, embolic myocardial infarction, peripheral artery occlusion and acute pulmonary embolism

Cardiovascular death between groups12 months

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.

Total thrombus recurrence between groups12 months

Recurrence of thrombus on cardiac imaging control following a total thrombus regression during the follow-up

Major bleedings between groups12 months

International Bleeding Academic Research Consortium (BARC) types 3 to 5

Trial Locations

Locations (35)

CH Compiègne Noyon

🇫🇷

Compiègne, France

CHU Angers

🇫🇷

Angers, France

CH Chartres

🇫🇷

Chartres, France

CH Bastia

🇫🇷

Bastia, France

CHU La réunion NORD

🇷🇪

Saint-Denis, Réunion

AP-HM CHU La Timone

🇫🇷

Marseille, France

CHU Nice

🇫🇷

Nice, France

CHU Pitié-Salpêtrière

🇫🇷

Paris, France

Hôpital Cardiologique du Haut Lévêque

🇫🇷

Bordeaux, France

CHU Brest

🇫🇷

Brest, France

CHU Gabriel Montpied

🇫🇷

Clermont-Ferrand, France

Hôpital Cardiovasculaire Louis Pradel

🇫🇷

Lyon, France

Hôpital Privé Dijon Bourgogne

🇫🇷

Dijon, France

CHU Lille

🇫🇷

Lille, France

CHR Metz-Thionville

🇫🇷

Metz, France

CHU Arnaud de Villeneuve

🇫🇷

Montpellier, France

AP-HP CHU Bichat

🇫🇷

Paris, France

AP-HP CHU Lariboisière

🇫🇷

Paris, France

CHU Nantes

🇫🇷

Nantes, France

Ap-Hp Hegp

🇫🇷

Paris, France

CH Francois Mitterand

🇫🇷

Pau, France

CHU Poitiers

🇫🇷

Potiers, France

CHU Rennes

🇫🇷

Rennes, France

CHU Strasbourg

🇫🇷

Strasbourg, France

CHU Toulouse

🇫🇷

Toulouse, France

Centre Hopistalier de Valence

🇫🇷

Valence, France

Ch Bretagne Atlantique

🇫🇷

Vannes, France

Ch Auxerre

🇫🇷

Auxerre, France

Groupe Hospitalier Mutualiste

🇫🇷

Grenoble, France

AP-HP Hopital Ambroise Paré

🇫🇷

Paris, France

Centre Cardiologique du Nord

🇫🇷

Saint-Denis, France

CHU de Nimes

🇫🇷

Nîmes, France

Ch Avignon

🇫🇷

Avignon, France

CHU Limoges

🇫🇷

Limoges, France

Clinique du Millenaire

🇫🇷

Montpellier, France

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