Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban In Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure "ADRIFT"

Recruiting

Phase 2/3 Results N/A

Trial Description

Evaluation of 2 doses of rivaroxaban (10 and 15 mg) compared to dual anti platelet therapy (aspirin+clopidogrel) after left atrial appendage closure. The patients will be assessed at 10 and 90 days: central laboratory hemostasis analysis and clinical events assessment.

Detailed Description

Data on antithrombotic therapy after Left Atrial Appendage Closure (LAAC) are scarce and no randomized evaluation has been performed to demonstrate what is the best antithrombotic strategy following LAAC. LAAC is classically associated with a 6-week period of anticoagulation with warfarin + aspirin followed by once daily clopidogrel (75 mg) + aspirin (81-325 mg) until the 6 months visit, then aspirin alone is continued indefinitely, as tested in patients without contraindication for anticoagulation in the pivotal Watchman trials. LAAC is mostly used in Europe as an alternative to warfarin anticoagulation when patients have a contraindication to or are unsuitable for warfarin anticoagulation. The classic regimen is not applicable and believed to be too risky in such frail patients. These patients usually receive a regimen of daily clopidogrel + aspirin followed by single antiplatelet therapy (most frequently used treatment). Some patients receive oral anticoagulation without aspirin, including NOAC anticoagulation. Rivaroxaban is a tempting strategy for anticoagulation following LAAC in atrial fibrillation (AF) patients. The dose needs first to be carefully evaluated the trial propose a dose ranging study in patients who have undergone successful LAAC.
The study will evaluate two different Rivaroxaban regimen (10 or 15 mg a day) in comparison to dual antiplatelet therapy (DAPT) (aspirin+clopidogrel : control arm representing standard of care) after successful LAAC. The aim is to investigate whether rivaroxaban could provide correct anticoagulation levels and adequately suppress coagulation activation after LAAC.
The patient will be enrolled after left atrial appendage closure before discharge. The randomization is 1/1/1 between the 3 groups : rivaroxaban 10mg a day, rivaroxaban 15 mg a day and aspirin 75mg + clopidogrel 75 mg a day. At 10 and 90 days, the patients will be sampled for biological assessment : Prothrombin fragments 1+2, Factor Xa inhibitory activity, Russel Viper venom enzyme assay, thrombin anti-thrombin (TAT) complex, D-Dimers, Prothrombin time (Neoplastin) and plasma von Willebrand factor (vWf) Ag level
After 90 days, the patient will end his/her participation in the trial. Clinical endpoints (death, MI, Stroke, TIA, systemic embolism, extracranial major bleeding or clinically relevant non major bleeding) at 90 days will be assessed by a clinical endpoint committee. Central echographic laboratory will review all 90 days transesophageal echocardiography (TEE) to detect the presence of thrombus or peri-device leak.
The study is open-label. Central laboratory, clinical endpoint committee and echographic core laboratory is blinded to randomization arm.

Conditions

Interventions

  • Rivaroxaban 10 mg qd Drug
    Intervention Desc: 10mg qd
    ARM 1: Kind: Experimental
    Label: 1: Rivaroxaban 10 mg qd
    Description: Rivaroxaban 10 mg, 1 tablet a day, from randomization to Day 90 should be taken between 8 and 10 AM
  • Rivaroxaban 15 mg qd Drug
    Intervention Desc: 15mg qd
    ARM 1: Kind: Experimental
    Label: 2: Rivaroxaban 15 mg qd
    Description: Rivaroxaban 15 mg, 1 tablet a day, from randomization to Day 90 should be taken between 8 and 10 AM
  • DAPT Drug
    Intervention Desc: Aspirin 75 mg qd + Clopidogrel 75 mg qd
    ARM 1: Kind: Experimental
    Label: 3: DAPT
    Description: Aspirin 75 mg, 1 a day Clopidogrel 75 mg, 1 tablet a day from randomization to Day 90 should be taken between 8 and 10 AM

Outcomes

Type Measure Time Frame Safety Issue
Primary Measure of prothrombin fragment 1 + 2 at Day 10
Secondary Factor Xa inhibitory activity at Day 10
Secondary Russel Viper venom enzyme assay at Day 90
Secondary TAT complex at Day 10
Secondary D-Dimers at Day 10
Secondary Prothrombin time (Neoplastin) at Day 10
Secondary Plasma vWf Ag level at Day 10
Secondary Haemorrhagic stroke and bleeding will be safety outcomes TEE with central core lab reading: presence of thrombus, peri-device leak at Day 90
Secondary Composite clinical endpoint combining all clinical outcomes : Death, MI, stroke, TIA, at Day 90
Secondary Death (any cause) at Day 90
Secondary Myocardial infarction (MI) at Day 90
Secondary Stroke (ischaemic stroke, haemorrhagic stroke) at Day 90
Secondary Transient Ischemic Attack (TIA) at Day 90
Secondary Systemic embolism at Day 90
Secondary Extracranial major bleeding or clinically relevant non major bleeding (ISTH definition) at Day 90

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