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)

This study has been completed.
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01674647
First received: August 27, 2012
Last updated: April 10, 2015
Last verified: April 2015
Results First Received: January 8, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Condition: Atrial Fibrillation
Interventions: Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Vitamin K antagonist (VKA)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 141 centers (involving 144 investigators) in Europe, South Africa, North America, and Asia Pacific.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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).

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) 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.
Vitamin K Antagonist (VKA) 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.

Participant Flow for 2 periods

Period 1:   Treatment Period
    Rivaroxaban (Xarelto, BAY59-7939)     Vitamin K Antagonist (VKA)  
STARTED     1002     502  
Subjects Received Treatment     988     499  
COMPLETED     846     400  
NOT COMPLETED     156     102  
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 2:   30-day Safety Follow-up Period
    Rivaroxaban (Xarelto, BAY59-7939)     Vitamin K Antagonist (VKA)  
STARTED     982     487  
COMPLETED     924     446  
NOT COMPLETED     58     41  
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  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) 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.
Vitamin K Antagonist (VKA) 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 Total of all reporting groups

Baseline Measures
    Rivaroxaban (Xarelto, BAY59-7939)     Vitamin K Antagonist (VKA)     Total  
Number of Participants  
[units: participants]
  1002     502     1504  
Age  
[units: years]
Mean (Standard Deviation)
  64.9  (10.6)     64.7  (10.5)     64.9  (10.5)  
Gender  
[units: Participants]
     
Female     275     135     410  
Male     727     367     1094  
CHADS 2 score [1]
[units: units on scale]
Mean (Standard Deviation)
  1.3  (1.1)     1.4  (1.1)     1.4  (1.1)  
CHA 2 DS 2 VASc score [2]
[units: units on scale]
Mean (Standard Deviation)
  2.3  (1.6)     2.3  (1.6)     2.3  (1.6)  
[1] 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.
[2] 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.



  Outcome Measures
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1.  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   [ 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 ]

2.  Primary:   Number of Participants With Major Bleedings as Per Central Adjudication   [ Time Frame: From randomization up to the date of the last dose of study drug + 2 days ]

3.  Secondary:   Number of Participants With Composite of Strokes and Non-central Nervous System Systemic Embolisms   [ 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 ]

4.  Secondary:   Number of Participants With Composite of Strokes, Transient Ischemic Attacks, Non-central Nervous System Systemic Embolisms, Myocardial Infarctions and All-cause Mortality   [ 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 ]

5.  Secondary:   Number of Participants With Strokes   [ 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 ]

6.  Secondary:   Number of Participants With Transient Ischemic Attacks   [ 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 ]

7.  Secondary:   Number of Participants With Non-central Nervous System Systemic Embolisms   [ 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 ]

8.  Secondary:   Number of Participants With Myocardial Infarctions   [ 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 ]

9.  Secondary:   Number of Participants With Cardiovascular Deaths   [ 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 ]

10.  Secondary:   Number of Participants With All-cause Mortality   [ 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 ]

11.  Secondary:   Number of Participants With Composite of Major and Non-major Bleeding Events   [ Time Frame: From randomization up to the date of the last dose of study drug + 2 days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Bayer HealthCare AG
Organization: Bayer HealthCare AG
e-mail: clinical-trials-contact@bayerhealthcare.com


Publications:

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01674647     History of Changes
Other Study ID Numbers: 15693, 2011-002234-39
Study First Received: August 27, 2012
Results First Received: January 8, 2015
Last Updated: April 10, 2015
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
China: Food and Drug Administration
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ministry of Health and Welfare
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Portugal: National Pharmacy and Medicines Institute
Singapore: Health Sciences Authority
South Africa: Department of Health
Spain: Ministry of Health, Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration