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

Last updated: December 20, 2021
Sponsor: Assistance Publique - Hôpitaux de Paris
Overall Status: Completed

Phase

2/3

Condition

Hemorrhage

Chest Pain

Cardiac Disease

Treatment

N/A

Clinical Study ID

NCT03273322
P161102J
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Men and women ≥18 years of age
  • Patients who underwent a clinically successful LAAC procedure (device implantedwithout procedural or bleeding complication). LAAC may have been indicated forpatients contraindicated or unsuitable for long-term Vitamin K antagonists (VKA)anticoagulation.
  • AF (permanent or persistent or paroxysmal) patients irrespective of priorantithrombotic treatment are eligible for randomization.
  • Written informed consent by the patient or designee if the patient is unable toconsent
  • Patients affiliated to the French social security system

Exclusion

Exclusion Criteria:

  • Creatinine clearance <30 mL / min (Cockcroft formula).
  • Dialysis.
  • Mechanical heart valves or valvular disease requiring surgery or interventionalprocedure
  • Planned Ablation of AF during follow up period
  • Mandatory indication for dual antiplatelet therapy (e.g. recent stent) or singleanti-platelet treatment (SAPT) (e.g. high coronary risk).
  • Any contra-indication or known allergy to aspirin or clopidogrel or rivaroxaban.
  • Any mandatory indication for anticoagulation for a reason other than AF (e.g.Pulmonary embolism)
  • Ongoing major bleeding or complicated or recent (<72hours) major surgery
  • Known large oesophageal varices or decompensated liver disease (unless a documentedpositive opinion of a gastro-enterologist)
  • Severe thrombocytopenia (<50,000/ml) after referral to haematologist to confirm or notcontraindication
  • Recent myocardial infarction (<6 weeks).
  • Recent cerebro-vascular event (CVE) or transient ischemic attack (<6 weeks) afterevaluation of stroke vs bleeding risk by the referring neurologist.
  • Recent Intracranial bleeding (< 6 months): these patients will be evaluated by aneurologist as these patients may be considered at higher stroke risk. Neurologist mayconsider that the LAAC procedure with a short (90 days) period of anticoagulation orantiplatelet therapy as tested in the protocol is a preferable option (in that caseintracranial hemorrhage (ICH) will not be considered as a contraindication).
  • Prasugrel or ticagrelor concomitant use
  • Participating in an investigational drug or another device trial within the previous 30 days.
  • High likelihood of being unavailable for follow-up or psycho-social condition makingstudy participation impractical.
  • Woman with child bearing potential who do not use an efficient method ofcontraception.
  • positive serum or urine pregnancy test for woman with child bearing potential
  • Pregnancy or within 48 hours post-partum or breast feeding women
  • Patient under legal protection

Study Design

Total Participants: 105
Study Start date:
September 13, 2017
Estimated Completion Date:
September 30, 2019

Study 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.

Connect with a study center

  • Institut de Cardiologie - Hôpital Pitié-Salpêtrière

    Paris, 75013
    France

    Site Not Available

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