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

NCT ID: NCT03273322

Last Updated: 2021-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-13
• Study Completion Date: 2019-09-30

Brief 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.

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

Atrial Fibrillation; Atrial Appendage; Hemorrhage

Keywords

Left atrial appendage closure; Rivaroxaban; Dual antiplatelet therapy; Anticoagulation; Stroke prevention

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1: Rivaroxaban 10 mg qd

Rivaroxaban 10 mg, 1 tablet a day, from randomization to Day 90 should be taken between 8 and 10 AM

Group Type: EXPERIMENTAL

Rivaroxaban 10 mg qd

Intervention Type: DRUG

10mg qd

2: Rivaroxaban 15 mg qd

Rivaroxaban 15 mg, 1 tablet a day, from randomization to Day 90

should be taken between 8 and 10 AM

Group Type: EXPERIMENTAL

Rivaroxaban 15 mg qd

Intervention Type: DRUG

15mg qd

3: DAPT

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

Group Type: ACTIVE_COMPARATOR

DAPT

Intervention Type: DRUG

Aspirin 75 mg qd + Clopidogrel 75 mg qd

Interventions

Rivaroxaban 10 mg qd

10mg qd

Intervention Type: DRUG

Rivaroxaban 15 mg qd

15mg qd

Intervention Type: DRUG

DAPT

Aspirin 75 mg qd + Clopidogrel 75 mg qd

Intervention Type: DRUG

Other Intervention Names

Experimental; Experimental; Active comparator

Eligibility Criteria

Inclusion Criteria

• Men and women ≥18 years of age
• Patients who underwent a clinically successful LAAC procedure (device implanted without procedural or bleeding complication). LAAC may have been indicated for patients contraindicated or unsuitable for long-term Vitamin K antagonists (VKA) anticoagulation.
• AF (permanent or persistent or paroxysmal) patients irrespective of prior antithrombotic treatment are eligible for randomization.
• Written informed consent by the patient or designee if the patient is unable to consent
• Patients affiliated to the French social security system

Exclusion Criteria

• Creatinine clearance <30 mL / min (Cockcroft formula).
• Dialysis.
• Mechanical heart valves or valvular disease requiring surgery or interventional procedure
• Planned Ablation of AF during follow up period
• Mandatory indication for dual antiplatelet therapy (e.g. recent stent) or single anti-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 documented positive opinion of a gastro-enterologist)
• Severe thrombocytopenia (<50,000/ml) after referral to haematologist to confirm or not contraindication
• Recent myocardial infarction (<6 weeks).
• Recent cerebro-vascular event (CVE) or transient ischemic attack (<6 weeks) after evaluation of stroke vs bleeding risk by the referring neurologist.
• Recent Intracranial bleeding (< 6 months): these patients will be evaluated by a neurologist as these patients may be considered at higher stroke risk. Neurologist may consider that the LAAC procedure with a short (90 days) period of anticoagulation or antiplatelet therapy as tested in the protocol is a preferable option (in that case intracranial 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 making study participation impractical.
• Woman with child bearing potential who do not use an efficient method of contraception.
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Action Research Group

OTHER

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilles MONTALESCOT, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Pitié-Salpêtrière Paris

Locations

Institut de Cardiologie - Hôpital Pitié-Salpêtrière

Paris, , France

Countries

France

References

Duthoit G, Silvain J, Marijon E, Ducrocq G, Lepillier A, Frere C, Dimby SF, Popovic B, Lellouche N, Martin-Toutain I, Spaulding C, Brochet E, Attias D, Mansourati J, Lorgis L, Klug D, Zannad N, Hauguel-Moreau M, Braik N, Deltour S, Ceccaldi A, Wang H, Hammoudi N, Brugier D, Vicaut E, Juliard JM, Montalescot G. Reduced Rivaroxaban Dose Versus Dual Antiplatelet Therapy After Left Atrial Appendage Closure: ADRIFT a Randomized Pilot Study. Circ Cardiovasc Interv. 2020 Jul;13(7):e008481. doi: 10.1161/CIRCINTERVENTIONS.119.008481. Epub 2020 Jul 17.

Reference Type: DERIVED

PMID: 32674675 (View on PubMed)

Other Identifiers

P161102J

Identifier Type: -

Identifier Source: org_study_id