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

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2011-002234-39-DK
• Date of registration: 19/09/2012
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG
• Public title: 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
• Scientific title: A prospective, randomized, open-label, parallel-group, active-controlled, multicenter study exploring the efficacy and safety of once-daily oral rivaroxaban (BAY 59-7939) compared with that of dose-adjusted oral vitamin K antagonists (VKA) for the prevention of cardiovascular events in subjects with nonvalvular atrial fibrillation scheduled for cardioversion
• Date of first enrolment: 19/09/2012
• Target sample size: 1500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002234-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: VKA Number of treatment arms in the trial: 2

Countries of recruitment

Belgium, Brazil, Canada, China, Denmark, Finland, France, Germany, Greece, Italy, Netherlands, Portugal, Singapore, South Africa, Spain, United Kingdom, United States

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer HealthCare AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer HealthCare AG

Key inclusion & exclusion criteria

Inclusion criteria:
• Men or women aged = 18 years
• Hemodynamically stable nonvalvular atrial fibrillation longer than 48 hours or of unknown duration
• Scheduled for cardioversion (electrical or pharmacological) of nonvalvular atrial fibrillation
• Written informed consent
• Women of childbearing potential and men must agree to use adequate contraception when sexually active. This applies from the time of signing of the informed consent form until 30 days after the last study drug administration. The definition of adequate contraception will be based on the judgment of the investigator and local requirements. Acceptable methods of contraception include (i) condoms (male or female) with or without a spermicidal agent; (ii) diaphragm or cervical cap with spermicide; (iii) intrauterine device; and (iv) hormone-based contraception.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 700
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 800

Exclusion criteria:
• Severe, disabling stroke (modified Rankin score of 4?5, inclusive; see Section 14.2) within 3 months or any stroke within 14 days before the randomization visit
• Transient ischemic attack within 3 days prior to randomization
• Acute thromboembolic events or thrombosis (venous/arterial) within the last 14 days prior to randomization
• Acute MI within the last 14 days prior to randomization
• Cardiac-related criteria:
o Known presence of left atrial/LAA thrombus before study inclusion
o Known presence of atrial myxoma
o Known left ventricular or aortic thrombus
o Valvular heart disease (either hemodynamically significant mitral valve stenosis or prosthetic heart valve)
• Active bleeding or high risk for bleeding contraindicating anticoagulant therapy
• Concomitant drugs/therapies:
o Indication for anticoagulant therapy for a condition other than atrial fibrillation (eg, VTE)
o Chronic aspirin therapy > 100 mg daily or dual antiplatelet therapy
o Concomitant use of strong inhibitors of both cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), ie, all human immunodeficiency virus protease inhibitors and the following azole antimycotic agents: ketoconazole, itraconazole, voriconazole, posaconazole, if used systemically
• Concomitant conditions:
o Childbearing potential without proper contraceptive measures, pregnancy, or breast feeding
o Hypersensitivity to investigational treatment or comparator treatment
o Calculated CrCl < 30 mL/minute (see Section 14.1)
o Hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk
o Any severe condition that would limit life expectancy to less than 6 months (eg, advanced malignancy, etc.)
o Planned invasive procedure with potential for uncontrolled bleeding, including major surgery or cardiac catheterization
o Inability to take oral medication
o Ongoing drug addiction or alcohol abuse
• Any other contraindication listed in the local labeling for the comparator treatment or experimental treatment
• Participation in a study with an investigational drug or medical device within 30 days prior to randomization
• Previous randomization in this study
• Inability to cooperate with the study procedures


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

prevention of stroke and non-central nervous system systemic embolism in subjects with non-valvular atrial fibrillation scheduled for cardioversion
MedDRA version: 14.1 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders

Intervention(s)

Trade Name: Xarelto
Product Name: Rivaroxaban
Product Code: BAY 59-7939
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RIVAROXABAN
CAS Number: 366789-02-8
Current Sponsor code: BAY 59-7939
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 20-

Trade Name: Xarelto
Product Name: Rivaroxaban
Product Code: BAY 59-7939
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RIVAROXABAN
CAS Number: 366789-02-8
Current Sponsor code: BAY 59-7939
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Product Name: a vitamin K antagonist (VKA) used according to standard of care
Pharmaceutical Form: Tablet

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint variable is the composite of the following efficacy outcomes (adjudicated centrally): stroke, transient ischemic attack, non-central nervous system systemic embolism, myocardial infarction and cardiovascular death.
The primary safety endpoint variable is major bleeding (as per central adjudication)

Timepoint(s) of evaluation of this end point: From randomization date up to the date of the last dose of study medication + 2 calendar days for subjects who complete the planned study medication period (about 45-49 days in direct cardiversion strategy, 65-100 days in delayed cardioversion arm)

For Safety endpoint from the date of first administration of study medication up to the date of the last study medication administration +2 calendar days for subjects who complete planned study (about 45-49 days in direct cardiversion strategy, 65-100 days in delayed arm)

Secondary Objective: Secondary objectives are to explore rivaroxaban treatment as compared with dose-adjusted VKA treatment with regard to the composite efficacy endpoint of stroke, TIA, non-central nervous system (CNS) systemic embolism, MI, and all-cause mortality (including cardiovascular death); the individual efficacy endpoints of all stroke, TIA, non-CNS systemic embolism, MI, cardiovascular death, and all-cause mortality (including cardiovascular death); and all bleeding events (major and non-major bleeding events).

Main Objective: The primary efficacy and safety objectives are to explore the efficacy of rivaroxaban compared with that of dose-adjusted vitamin K antagonists (VKA) in the prevention of the events with regard to the combined efficacy endpoint of all stroke or transient ischemic attack (TIA), non-central nervous system (CNS) systemic embolism, myocardial infarction (MI), and cardiovascular death in subjects with atrial fibrillation scheduled for cardioversion; and to explore the safety of rivaroxaban compared with dose-adjusted VKA with regard to the safety endpoint of major bleeding events in subjects with atrial fibrillation scheduled for cardioversion.

Secondary Outcome(s)

Secondary end point(s): Composite of stroke and non-central nervous system systemic embolism

Composite of stroke, transient ischemic attack, non-central nervous system systemic embolism, myocardial infarction, all- cause mortality

Stroke
Transient ischemic attack
Non-central nervous system systemic embolism
Myocardial infarction
Cardiovascular death
All cause mortality

Timepoint(s) of evaluation of this end point: From randomization date up to the date of the last dose of study medication + 2 calendar days for subjects who complete the planned study medication period (about 45-49 days in direct cardiversion strategy, 65-100 days in delayed cardioversion arm)

Secondary ID(s)

BAY59-7939/15693

2011-002234-39-FI

Source(s) of Monetary Support

Janssen Research and Development, LLC

Bayer HealthCare AG