Explore the Efficacy and Safety of Once-daily Oral Rivaroxaban for the Prevention of Cardiovascular Events in Subjects With Nonvalvular Atrial Fibrillation Scheduled for Cardioversion "X-VERT"

Completed

Phase 3 Results

Trial Description

A study for patients with abnormal heart rhythm (atrial fibrillation) who need to undergo cardioversion (procedure to restore normal heart rhythm). The study will compare patients assigned randomly (like flipping a coin) to either Rivaroxaban or vitamin K antagonist (VKA). The study will measure common medical outcomes for this type of patient such as bleeding and stroke.

Conditions

Interventions

  • Rivaroxaban (Xarelto, BAY59-7939) Drug
    Intervention Desc: Rivaroxaban 20 mg orally once daily; subjects with moderate renal impairment (ie, CrCl of 30 to 49 mL/min, inclusive) will receive the adjusted dose of 15 mg orally once daily in the study
    ARM 1: Kind: Experimental
    Label: Rivaroxaban (Xarelto, BAY59-7939)
    Description: A Direct Cardioversion Strategy can be performed only if sufficient anticoagulation is proven during the last 21 days prior to randomization and/or a transesophageal echocardiogram (TEE) is planned before cardioversion. Rivaroxaban will be given for 1-5 days before planned direct cardioversion. The run-in of 1-5 days is needed due to potential pretreatment with VKA. Treatment with rivaroxaban will be continued for 42 days after the cardioversion. A Delayed Cardioversion Strategy will be chosen if sufficient anticoagulation is not proven during the last 21 days prior to randomization and no TEE is planned. Rivaroxaban will be given for at least 21 (+4) days before the planned cardioversion, to a maximum of 56 (+4) days prior to planned cardioversion.
  • Vitamin K antagonist (VKA) Drug
    Intervention Desc: VKA orally once daily titrated to a target international normalized ratio (INR) of 2.5 (range 2.0-3.0, inclusive); the VKA type (eg, warfarin, acenocoumarol, phenprocoumon, fluindione, etc) will be assigned by the investigator according to local treatment standards
    ARM 1: Kind: Experimental
    Label: Vitamin K antagonist (VKA)
    Description: A Direct Cardioversion Strategy can be performed only if sufficient anticoagulation is proven during the last 21 days prior to randomization and/or a transesophageal echocardiogram (TEE) is planned before cardioversion. VKA will be given for 1-5 days before planned direct cardioversion. The run-in of 1-5 days is needed due to potential pretreatment with VKA. Treatment with VKA will be continued for 42 days after the cardioversion. A Delayed Cardioversion Strategy will be chosen if sufficient anticoagulation is not proven during the last 21 days prior to randomization and no TEE is planned. VKA will be given for at least 21 (+4) days before the planned cardioversion, to a maximum of 56 (+4) days prior to planned cardioversion.

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Prevention
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Composite number of the following events, adjudicated centrally: stroke, transient ischemic attack, non-central nervous system systemic embolism, myocardial infarction and cardiovascular death Up to 100 days No
Primary Number of major bleedings as per central adjudication Up to 100 days Yes
Secondary Composite number of strokes and non-central nervous system systemic embolisms Up to 100 days No
Secondary Composite number of strokes, transient ischemic attacks, non-central nervous system systemic embolisms, myocardial infarctions and all-cause mortality Up to 100 days No
Secondary Number of strokes Up to 100 days No
Secondary Number of transient ischemic attacks Up to 100 days No
Secondary Number of non-central nervous system systemic embolisms Up to 100 days No
Secondary Number of myocardial infarctions Up to 100 days No
Secondary Number of cardiovascular deaths Up to 100 days No
Secondary All-cause mortality Up to 100 days No
Secondary Composite number of major and non-major bleeding events Up to 100 days Yes
Primary Number of Participants With Composite of the Following Events, Adjudicated Centrally: Stroke, Transient Ischemic Attack, Non-central Nervous System Systemic Embolism, Myocardial Infarction and Cardiovascular Death From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment No
Primary Number of Participants With Major Bleedings as Per Central Adjudication From randomization up to the date of the last dose of study drug + 2 days Yes
Secondary Number of Participants With Composite of Strokes and Non-central Nervous System Systemic Embolisms From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment No
Secondary Number of Participants With Composite of Strokes, Transient Ischemic Attacks, Non-central Nervous System Systemic Embolisms, Myocardial Infarctions and All-cause Mortality From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment No
Secondary Number of Participants With Strokes From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment No
Secondary Number of Participants With Transient Ischemic Attacks From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment No
Secondary Number of Participants With Non-central Nervous System Systemic Embolisms From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment No
Secondary Number of Participants With Myocardial Infarctions From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment No
Secondary Number of Participants With Cardiovascular Deaths From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment No
Secondary Number of Participants With All-cause Mortality From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment No
Secondary Number of Participants With Composite of Major and Non-major Bleeding Events From randomization up to the date of the last dose of study drug + 2 days Yes

Sponsors