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

Phase 3Active Not RecruitingNCT05825573

Centre Hospitalier Universitaire de Nīmes340 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Interventions

Vitamin K antagonistDRUG

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 anticoagulantDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (35)

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

...and 25 more locations

Outcomes

Primary Outcomes

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)

Time frame: 6 months

Secondary Outcomes

All cause death between groups

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

Time frame: 6 months

All cause death between groups

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

Time frame: 12 months

Myocardial infarction occurrence between groups

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

Time frame: 6 months

Myocardial infarction occurrence between groups

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

Time frame: 12 months

Stroke occurrence between groups

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

Time frame: 6 months

Stroke occurrence between groups

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

Time frame: 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

Time frame: 6 months

Acute peripheral emboli occurrence between groups

Time frame: 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

Time frame: 6 months

Acute pulmonary embolism occurrence between groups

Time frame: 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

Time frame: 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

Time frame: 12 months

Clinically relevant bleedings between groups

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

Time frame: 6 months

Clinically relevant bleedings between groups

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

Time frame: 12 months

Systemic embolism between groups

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

Time frame: 6 months

Systemic embolism between groups

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

Time frame: 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.

Time frame: 6 months

Cardiovascular death between groups

Time frame: 12 months

Total thrombus recurrence between groups

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

Time frame: 6 months

Total thrombus recurrence between groups

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

Time frame: 12 months

Major bleedings between groups

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

Time frame: 6 months

Major bleedings between groups

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

Time frame: 12 months

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

Overview

Conditions

Interventions

Eligibility

Locations (35)

Outcomes

Primary Outcomes

Secondary Outcomes