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Trial record 97 of 156 for:    warfarin AND Vitamin K

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)

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ClinicalTrials.gov Identifier: NCT01674647
Recruitment Status : Completed
First Posted : August 29, 2012
Results First Posted : February 3, 2015
Last Update Posted : April 30, 2015
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Atrial Fibrillation
Interventions Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Vitamin K antagonist (VKA)
Enrollment 1504
Recruitment Details The study was conducted at 141 centers (involving 144 investigators) in Europe, South Africa, North America, and Asia Pacific.
Pre-assignment Details Overall, 1584 subjects were screened and 80 subjects did not complete or pass screening. 1504 subjects were randomized; 1002 were assigned to rivaroxaban and 502 to vitamin K antagonist (VKA).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Vitamin K Antagonist (VKA)
Hide Arm/Group Description Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period. Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Period Title: Treatment Period
Started 1002 502
Subjects Received Treatment 988 499
Completed 846 400
Not Completed 156 102
Reason Not Completed
Death             4             1
Efficacy outcome reached             0             1
Physician Decision             3             1
Adverse Event             60             22
Non-compliance with study drug             3             0
Lost to Follow-up             1             1
Withdrawal by Subject             19             16
Switching to other therapy             5             2
Logistical difficulties             5             8
Treatment failure             0             14
Protocol Violation             56             36
Period Title: 30-day Safety Follow-up Period
Started 982 487
Completed 924 446
Not Completed 58 41
Reason Not Completed
Death             3             2
Non-compliance with study drug             0             1
Protocol Violation             39             22
Logistical difficulties             1             3
Withdrawal by Subject             7             8
Lost to Follow-up             8             5
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Vitamin K Antagonist (VKA) Total
Hide Arm/Group Description Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period. Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period. Total of all reporting groups
Overall Number of Baseline Participants 1002 502 1504
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1002 participants 502 participants 1504 participants
64.9  (10.6) 64.7  (10.5) 64.9  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1002 participants 502 participants 1504 participants
Female
275
  27.4%
135
  26.9%
410
  27.3%
Male
727
  72.6%
367
  73.1%
1094
  72.7%
CHADS 2 score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on scale
Number Analyzed 1002 participants 502 participants 1504 participants
1.3  (1.1) 1.4  (1.1) 1.4  (1.1)
[1]
Measure Description: Predicts clinical risk of stroke and thromboembolism in atrial fibrillation incorporating these risk factors: Congestive heart failure, Hypertension, Age [greater than or equal to (>=)75 years], Diabetes mellitus, Stroke/transient ischemic attack. Total score ranged from 0 to 6, with "0"= low risk, "1"= moderate risk and ">=2"= high risk.
CHA 2 DS 2 VASc score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on scale
Number Analyzed 1002 participants 502 participants 1504 participants
2.3  (1.6) 2.3  (1.6) 2.3  (1.6)
[1]
Measure Description: Predicts clinical risk of stroke and thromboembolism in atrial fibrillation incorporating these risk factors: Congestive heart failure/left ventricular dysfunction, Hypertension, Age >= 75 years, Diabetes mellitus, Stroke/transient ischemic attack/thromboembolism, Vascular disease (prior myocardial infarction, peripheral artery disease, or aortic plaque), Age 65 - 74 years, Sex category (i.e., female). Total score ranged from 0 to 8, with "0" (or 1 if female only)= Low risk ; "1" (except for female gender alone)= moderate risk and ">=2"=high risk.
1.Primary Outcome
Title 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
Hide Description Stroke, TIA, Non-CNS Embolism, MI and cardiovascular death were adjudicated and confirmed by Clinical Endpoints Committee (CEC). Stroke included hemorrhagic and ischemic infarction. TIA including information if with or without matching lesion. Non CNS systemic embolism included emboli in peripheral arterial of the upper and lower extremities, ocular and retinal (pulmonary embolism and MI were excluded from the category). MI was assessed based on either cardiac biomarkers, new abnormal Q waves appeared on electrocardiogram for >= 2 leads, or autopsy confirmation. Cardiovascular death included death in subjects with non-valvular atrial fibrillation (AF). Number of subjects with composite events were reported.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The primary population for the efficacy analysis was the modified intention-to-treat (mITT) population. mITT population included all the randomized subjects in whom a left atrial/left atrial appendage (LA/LAA) thrombus was not diagnosed during a transesophageal echocardiogram (TEE) performed before the first planned cardioversion in the study.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Vitamin K Antagonist (VKA)
Hide Arm/Group Description:
Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.
Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Overall Number of Participants Analyzed 978 492
Measure Type: Number
Unit of Measure: Participants
5 5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Vitamin K Antagonist (VKA)
Comments Descriptive comparison of crude estimates of the cumulative incidence and estimation of risk ratio, all with 95% confidence intervals
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method no statistical test performed
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
0.15 to 1.73
Estimation Comments Crude estimate of the cumulative incidence for rivaroxaban (Xarelto, BAY59-7939): 0.51% (0.20% - 1.17%). Crude estimate of the cumulative incidence for Vitamin K antagonist (VKA): 1.02% (0.40% - 2.34%).
2.Primary Outcome
Title Number of Participants With Major Bleedings as Per Central Adjudication
Hide Description Bleeding events were adjudicated and confirmed by CEC blinded to treatment. The CEC categorized the bleeding events as major or non-major. The bleeding events were defined per the International Society on Thrombosis and Hemostasis (ISTH) criteria. Major bleeding was clinically overt bleeding associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or higher, leading to a transfusion of 2 or more units of packed red blood cells or whole blood, occurring in a critical site or contributing to death. Number of subjects with confirmed adjudicated bleeding events occurring in greater than (>)1 total subjects were reported.
Time Frame From randomization up to the date of the last dose of study drug + 2 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety profile was analyzed using the safety analysis set (SAF) population. SAF population included all randomized subjects who received at least 1 dose of study medication.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Vitamin K Antagonist (VKA)
Hide Arm/Group Description:
Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.
Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Overall Number of Participants Analyzed 988 499
Measure Type: Number
Unit of Measure: Participants
6 4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Vitamin K Antagonist (VKA)
Comments Descriptive comparison of crude estimates of the cumulative incidence and estimation of risk ratio, all with 95% confidence intervals
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method no test performed
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.21 to 2.67
Estimation Comments Crude estimate of the cumulative incidence for rivaroxaban (Xarelto, BAY59-7939): 0.61% (0.26% - 1.27%). Crude estimate of the cumulative incidence for Vitamin K antagonist (VKA): 0.80% (0.27% - 2.00%).
3.Secondary Outcome
Title Number of Participants With Composite of Strokes and Non-central Nervous System Systemic Embolisms
Hide Description Stroke and Non-CNS Embolism were adjudicated and confirmed by CEC. Stroke included hemorrhagic and ischemic infarction. Non CNS systemic embolism included emboli in peripheral arterial of the upper and lower extremities, ocular and retinal (pulmonary embolism and MI were excluded from the category). Number of subjects with composite events were reported.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Vitamin K Antagonist (VKA)
Hide Arm/Group Description:
Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.
Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Overall Number of Participants Analyzed 978 492
Measure Type: Number
Unit of Measure: Participants
2 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Vitamin K Antagonist (VKA)
Comments Descriptive comparison of crude estimates of the cumulative incidence and estimation of risk ratio, all with 95% confidence intervals
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method no statistical test performed
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.06 to 2.00
Estimation Comments Crude estimate of the cumulative incidence for rivaroxaban (Xarelto, BAY59-7939): 0.20% (0.04% - 0.71%). Crude estimate of the cumulative incidence for Vitamin K antagonist (VKA): 0.61% (0.17% - 1.72%).
4.Secondary Outcome
Title Number of Participants With Composite of Strokes, Transient Ischemic Attacks, Non-central Nervous System Systemic Embolisms, Myocardial Infarctions and All-cause Mortality
Hide Description Stroke, TIA, Non- CNS systemic embolism, MI and all-cause mortality were adjudicated and confirmed by CEC. Stroke included hemorrhagic and ischemic infarction. TIA including information if with or without matching lesion. Non CNS systemic embolism included emboli in peripheral arterial of the upper and lower extremities, ocular and retinal (pulmonary embolism and MI were excluded from the category). MI was assessed based on either cardiac biomarkers, new abnormal Q waves appeared on electrocardiogram for >= 2 leads, or autopsy confirmation. All-cause mortality included vascular death and non-vascular death. Number of subjects with composite events were reported.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Vitamin K Antagonist (VKA)
Hide Arm/Group Description:
Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.
Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Overall Number of Participants Analyzed 978 492
Measure Type: Number
Unit of Measure: Participants
6 6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Vitamin K Antagonist (VKA)
Comments Descriptive comparison of crude estimates of the cumulative incidence and estimation of risk ratio, all with 95% confidence intervals
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method no statistical test performed
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
0.16 to 1.55
Estimation Comments Crude estimate of the cumulative incidence for rivaroxaban (Xarelto, BAY59-7939): 0.61% (0.27% - 1.29%). Crude estimate of the cumulative incidence for Vitamin K antagonist (VKA): 1.22% (0.53% - 2.51%).
5.Secondary Outcome
Title Number of Participants With Strokes
Hide Description All events were adjudicated and confirmed by a CEC blinded to treatment. Stroke included hemorrhagic (Stroke with local collections of intraparenchymal blood. Subarachnoid hemorrhage, subdural hemorrhage, and epidural hemorrhage were excluded), ischemic infarction (Stroke without focal collection of intracranial blood) and unknown (No imaging data and anatomic findings were available). Number of subjects with strokes were reported.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Vitamin K Antagonist (VKA)
Hide Arm/Group Description:
Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.
Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Overall Number of Participants Analyzed 978 492
Measure Type: Number
Unit of Measure: Participants
2 2
6.Secondary Outcome
Title Number of Participants With Transient Ischemic Attacks
Hide Description All events were adjudicated and confirmed by a CEC blinded to treatment. Number of subjects with TIA were reported.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Vitamin K Antagonist (VKA)
Hide Arm/Group Description:
Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.
Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Overall Number of Participants Analyzed 978 492
Measure Type: Number
Unit of Measure: Participants
0 0
7.Secondary Outcome
Title Number of Participants With Non-central Nervous System Systemic Embolisms
Hide Description All events were adjudicated and confirmed by a CEC blinded to treatment. Non CNS systemic embolism included emboli in peripheral arterial of the upper and lower extremities, ocular and retinal (pulmonary embolism and MI were excluded from the category). Number of subjects with non-CNS embolism were reported.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Vitamin K Antagonist (VKA)
Hide Arm/Group Description:
Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.
Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Overall Number of Participants Analyzed 978 492
Measure Type: Number
Unit of Measure: Participants
0 1
8.Secondary Outcome
Title Number of Participants With Myocardial Infarctions
Hide Description All events were adjudicated and confirmed by a CEC blinded to treatment. MI was assessed based onmeither cardiac biomarkers, new abnormal Q waves appeared on electrocardiogram for >= 2 leads, or autopsy confirmation. Number of subjects with MI were reported.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Vitamin K Antagonist (VKA)
Hide Arm/Group Description:
Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.
Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Overall Number of Participants Analyzed 978 492
Measure Type: Number
Unit of Measure: Participants
1 1
9.Secondary Outcome
Title Number of Participants With Cardiovascular Deaths
Hide Description All events were adjudicated and confirmed by a CEC blinded to treatment. Any death that was not clearly non-vascular (e.g., deaths due to spontaneous bleeding, myocardial infarction, stroke, cardiac failure, and arrhythmia). Number of subjects with cardiovascular deaths were reported.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Vitamin K Antagonist (VKA)
Hide Arm/Group Description:
Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.
Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Overall Number of Participants Analyzed 978 492
Measure Type: Number
Unit of Measure: Participants
4 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Vitamin K Antagonist (VKA)
Comments Descriptive comparison of crude estimates of the cumulative incidence and estimation of risk ratio, all with 95% confidence intervals
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method no statistical test performed
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.18 to 5.47
Estimation Comments Crude estimate of the cumulative incidence for rivaroxaban (Xarelto, BAY59-7939): 0.41% (0.14% - 1.02%). Crude estimate of the cumulative incidence for Vitamin K antagonist (VKA): 0.41% (0.07% - 1.41%).
10.Secondary Outcome
Title Number of Participants With All-cause Mortality
Hide Description All events were adjudicated and confirmed by a CEC blinded to treatment. All-cause mortality included vascular death and non-vascular death. Number of subjects with all-cause mortality were reported.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Vitamin K Antagonist (VKA)
Hide Arm/Group Description:
Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.
Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Overall Number of Participants Analyzed 978 492
Measure Type: Number
Unit of Measure: Participants
5 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Vitamin K Antagonist (VKA)
Comments Descriptive comparison of crude estimates of the cumulative incidence and estimation of risk ratio, all with 95% confidence intervals
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method no statistical test performed
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.20 to 3.49
Estimation Comments Crude estimate of the cumulative incidence for rivaroxaban (Xarelto, BAY59-7939): 0.51% (0.20% - 1.17%). Crude estimate of the cumulative incidence for Vitamin K antagonist (VKA): 0.61% (0.17% - 1.72%).
11.Secondary Outcome
Title Number of Participants With Composite of Major and Non-major Bleeding Events
Hide Description All events were adjudicated and confirmed by a CEC blinded to treatment. The CEC categorized the bleeding events as major or non-major. The bleeding events were defined per the ISTH criteria. Clinically relevant bleeding included major bleeding (overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of 2 or more units of packed red blood cells or whole blood, occurring in a critical site or contributing to death) and non-major bleeding associated with medical intervention, unscheduled physician contact, (temporary) cessation of study treatment, discomfort for the participants such as pain, or impairment of activities of daily life. Number of subjects with clinically relevant major and non-major bleeding events were reported.
Time Frame From randomization up to the date of the last dose of study drug + 2 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety profile was analyzed using the SAF population. SAF population included all randomized subjects who received at least 1 dose of study medication.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Vitamin K Antagonist (VKA)
Hide Arm/Group Description:
Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.
Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Overall Number of Participants Analyzed 988 499
Measure Type: Number
Unit of Measure: Participants
33 14
Time Frame From first administration of study drug to date of last study drug + 2 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rivaroxaban (Xarelto; BAY59-7939) Vitamin K Antagonist
Hide Arm/Group Description Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period. Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
All-Cause Mortality
Rivaroxaban (Xarelto; BAY59-7939) Vitamin K Antagonist
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Rivaroxaban (Xarelto; BAY59-7939) Vitamin K Antagonist
Affected / at Risk (%) Affected / at Risk (%)
Total   93/988 (9.41%)   38/499 (7.62%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/988 (0.10%)  0/499 (0.00%) 
Cardiac disorders     
Acute myocardial infarction * 1  1/988 (0.10%)  0/499 (0.00%) 
Angina pectoris * 1  2/988 (0.20%)  0/499 (0.00%) 
Arrhythmia supraventricular * 1  1/988 (0.10%)  0/499 (0.00%) 
Atrial fibrillation * 1  8/988 (0.81%)  4/499 (0.80%) 
Atrial flutter * 1  4/988 (0.40%)  1/499 (0.20%) 
Atrial tachycardia * 1  1/988 (0.10%)  0/499 (0.00%) 
Atrial thrombosis * 1  4/988 (0.40%)  3/499 (0.60%) 
Bradyarrhythmia * 1  1/988 (0.10%)  0/499 (0.00%) 
Bradycardia * 1  3/988 (0.30%)  3/499 (0.60%) 
Cardiac arrest * 1  3/988 (0.30%)  0/499 (0.00%) 
Cardiac failure * 1  8/988 (0.81%)  2/499 (0.40%) 
Cardiac failure acute * 1  1/988 (0.10%)  0/499 (0.00%) 
Cardiac failure chronic * 1  1/988 (0.10%)  0/499 (0.00%) 
Cardiac failure congestive * 1  10/988 (1.01%)  2/499 (0.40%) 
Cardiogenic shock * 1  0/988 (0.00%)  1/499 (0.20%) 
Cardiomyopathy * 1  0/988 (0.00%)  1/499 (0.20%) 
Coronary artery disease * 1  0/988 (0.00%)  1/499 (0.20%) 
Intracardiac thrombus * 1  1/988 (0.10%)  0/499 (0.00%) 
Mitral valve incompetence * 1  3/988 (0.30%)  0/499 (0.00%) 
Pericardial effusion * 1  1/988 (0.10%)  0/499 (0.00%) 
Rhythm idioventricular * 1  1/988 (0.10%)  0/499 (0.00%) 
Sick sinus syndrome * 1  0/988 (0.00%)  2/499 (0.40%) 
Sinus bradycardia * 1  0/988 (0.00%)  2/499 (0.40%) 
Tachycardia induced cardiomyopathy * 1  1/988 (0.10%)  0/499 (0.00%) 
Ventricular arrhythmia * 1  1/988 (0.10%)  0/499 (0.00%) 
Ventricular tachycardia * 1  1/988 (0.10%)  0/499 (0.00%) 
Eye disorders     
Blindness transient * 1  0/988 (0.00%)  1/499 (0.20%) 
Gastrointestinal disorders     
Abdominal pain * 1  4/988 (0.40%)  0/499 (0.00%) 
Constipation * 1  1/988 (0.10%)  0/499 (0.00%) 
Diarrhoea * 1  1/988 (0.10%)  0/499 (0.00%) 
Gastrointestinal haemorrhage * 1  1/988 (0.10%)  0/499 (0.00%) 
Haematochezia * 1  1/988 (0.10%)  0/499 (0.00%) 
Lower gastrointestinal haemorrhage * 1  1/988 (0.10%)  1/499 (0.20%) 
Nausea * 1  2/988 (0.20%)  0/499 (0.00%) 
Oesophagitis * 1  0/988 (0.00%)  1/499 (0.20%) 
Rectal haemorrhage * 1  2/988 (0.20%)  0/499 (0.00%) 
Upper gastrointestinal haemorrhage * 1  1/988 (0.10%)  2/499 (0.40%) 
Vomiting * 1  1/988 (0.10%)  0/499 (0.00%) 
General disorders     
Chest discomfort * 1  1/988 (0.10%)  1/499 (0.20%) 
Chest pain * 1  5/988 (0.51%)  0/499 (0.00%) 
Medical device site reaction * 1  0/988 (0.00%)  1/499 (0.20%) 
Non-cardiac chest pain * 1  1/988 (0.10%)  0/499 (0.00%) 
Infections and infestations     
Bronchitis * 1  1/988 (0.10%)  1/499 (0.20%) 
Bronchitis viral * 1  1/988 (0.10%)  0/499 (0.00%) 
Cellulitis * 1  2/988 (0.20%)  1/499 (0.20%) 
Diverticulitis * 1  0/988 (0.00%)  1/499 (0.20%) 
Gastroenteritis * 1  0/988 (0.00%)  1/499 (0.20%) 
Pharyngitis * 1  1/988 (0.10%)  0/499 (0.00%) 
Pneumonia * 1  2/988 (0.20%)  3/499 (0.60%) 
Pseudomembranous colitis * 1  1/988 (0.10%)  0/499 (0.00%) 
Urinary tract infection * 1  0/988 (0.00%)  1/499 (0.20%) 
Injury, poisoning and procedural complications     
Subdural haematoma * 1  0/988 (0.00%)  1/499 (0.20%) 
Wound haemorrhage * 1  1/988 (0.10%)  0/499 (0.00%) 
Investigations     
Arteriogram coronary * 1  0/988 (0.00%)  1/499 (0.20%) 
Electrocardiogram PR prolongation * 1  1/988 (0.10%)  0/499 (0.00%) 
Electrocardiogram T wave abnormal * 1  1/988 (0.10%)  0/499 (0.00%) 
Liver function test abnormal * 1  1/988 (0.10%)  0/499 (0.00%) 
Metabolism and nutrition disorders     
Hyponatraemia * 1  1/988 (0.10%)  0/499 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthritis reactive * 1  0/988 (0.00%)  1/499 (0.20%) 
Back pain * 1  0/988 (0.00%)  1/499 (0.20%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder neoplasm * 1  1/988 (0.10%)  0/499 (0.00%) 
Lung neoplasm malignant * 1  1/988 (0.10%)  0/499 (0.00%) 
Malignant pleural effusion * 1  1/988 (0.10%)  0/499 (0.00%) 
Nervous system disorders     
Carotid artery stenosis * 1  1/988 (0.10%)  0/499 (0.00%) 
Dizziness * 1  0/988 (0.00%)  1/499 (0.20%) 
Haemorrhage intracranial * 1  1/988 (0.10%)  0/499 (0.00%) 
Presyncope * 1  1/988 (0.10%)  0/499 (0.00%) 
Syncope * 1  2/988 (0.20%)  0/499 (0.00%) 
Thalamus haemorrhage * 1  1/988 (0.10%)  0/499 (0.00%) 
Psychiatric disorders     
Delirium * 1  1/988 (0.10%)  0/499 (0.00%) 
Renal and urinary disorders     
Haematuria * 1  1/988 (0.10%)  0/499 (0.00%) 
Renal failure acute * 1  0/988 (0.00%)  2/499 (0.40%) 
Urogenital haemorrhage * 1  0/988 (0.00%)  1/499 (0.20%) 
Reproductive system and breast disorders     
Vaginal haemorrhage * 1  1/988 (0.10%)  0/499 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema * 1  0/988 (0.00%)  1/499 (0.20%) 
Asthma * 1  1/988 (0.10%)  0/499 (0.00%) 
Dyspnoea * 1  4/988 (0.40%)  1/499 (0.20%) 
Pulmonary alveolar haemorrhage * 1  0/988 (0.00%)  1/499 (0.20%) 
Pulmonary congestion * 1  0/988 (0.00%)  1/499 (0.20%) 
Pulmonary fibrosis * 1  1/988 (0.10%)  0/499 (0.00%) 
Pulmonary hypertension * 1  1/988 (0.10%)  0/499 (0.00%) 
Pulmonary oedema * 1  1/988 (0.10%)  0/499 (0.00%) 
Respiratory disorder * 1  1/988 (0.10%)  0/499 (0.00%) 
Sleep apnoea syndrome * 1  1/988 (0.10%)  0/499 (0.00%) 
Surgical and medical procedures     
Bladder catheterisation * 1  0/988 (0.00%)  1/499 (0.20%) 
Cardiac ablation * 1  3/988 (0.30%)  1/499 (0.20%) 
Implantable defibrillator insertion * 1  1/988 (0.10%)  0/499 (0.00%) 
Plastic surgery * 1  0/988 (0.00%)  1/499 (0.20%) 
Shoulder arthroplasty * 1  1/988 (0.10%)  0/499 (0.00%) 
Vascular disorders     
Hypotension * 1  2/988 (0.20%)  0/499 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Rivaroxaban (Xarelto; BAY59-7939) Vitamin K Antagonist
Affected / at Risk (%) Affected / at Risk (%)
Total   272/988 (27.53%)   126/499 (25.25%) 
Cardiac disorders     
Atrial fibrillation * 1  2/988 (0.20%)  7/499 (1.40%) 
Atrial thrombosis * 1  16/988 (1.62%)  6/499 (1.20%) 
Atrioventricular block first degree * 1  40/988 (4.05%)  25/499 (5.01%) 
Bradycardia * 1  30/988 (3.04%)  13/499 (2.61%) 
Sinus bradycardia * 1  25/988 (2.53%)  12/499 (2.40%) 
Gastrointestinal disorders     
Constipation * 1  10/988 (1.01%)  3/499 (0.60%) 
Diarrhoea * 1  18/988 (1.82%)  3/499 (0.60%) 
Nausea * 1  17/988 (1.72%)  1/499 (0.20%) 
General disorders     
Fatigue * 1  14/988 (1.42%)  9/499 (1.80%) 
Oedema peripheral * 1  20/988 (2.02%)  5/499 (1.00%) 
Infections and infestations     
Influenza * 1  3/988 (0.30%)  5/499 (1.00%) 
Nasopharyngitis * 1  12/988 (1.21%)  5/499 (1.00%) 
Urinary tract infection * 1  7/988 (0.71%)  5/499 (1.00%) 
Injury, poisoning and procedural complications     
Contusion * 1  3/988 (0.30%)  5/499 (1.00%) 
Investigations     
International normalised ratio increased * 1  1/988 (0.10%)  9/499 (1.80%) 
Nervous system disorders     
Dizziness * 1  25/988 (2.53%)  9/499 (1.80%) 
Headache * 1  25/988 (2.53%)  7/499 (1.40%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  13/988 (1.32%)  3/499 (0.60%) 
Dyspnoea * 1  16/988 (1.62%)  12/499 (2.40%) 
Epistaxis * 1  30/988 (3.04%)  9/499 (1.80%) 
Skin and subcutaneous tissue disorders     
Rash * 1  12/988 (1.21%)  5/499 (1.00%) 
Vascular disorders     
Hypertension * 1  22/988 (2.23%)  4/499 (0.80%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.1)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Bayer HealthCare AG
Organization: Bayer HealthCare AG
EMail: clinical-trials-contact@bayerhealthcare.com
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01674647     History of Changes
Other Study ID Numbers: 15693
2011-002234-39 ( EudraCT Number )
First Submitted: August 27, 2012
First Posted: August 29, 2012
Results First Submitted: January 8, 2015
Results First Posted: February 3, 2015
Last Update Posted: April 30, 2015