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| ID | Type | Description | Link |
|---|---|---|---|
| RIVAROXAFL3002 | Other Identifier | Janssen Scientific Affairs, LLC | |
| 2012-001484-79 | EudraCT Number |
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| Name | Class |
|---|---|
| Bayer | INDUSTRY |
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The purpose of this exploratory study is to evaluate the safety of rivaroxaban and uninterrupted vitamin K antagonist (VKA) in adult participants with non-valvular atrial fibrillation (NVAF) who undergo catheter ablation as measured by post-procedure major bleeding events.
This is a randomized (participants are assigned to intervention groups by chance), open-label (both physicians and participants know the identity of the assigned treatment), active-controlled, multi-center safety study of rivaroxaban or VKA before and after a catheter ablation procedure. This study requires collaboration with medical institutions that provide access to electrophysiologists who normally perform the catheter ablation procedure. In this study, NVAF is to be defined as the presence of AF in a person who does not have a prosthetic heart valve (annuloplasty with or without prosthetic ring, commissurotomy and/or valvuloplasty are permitted) and who does not have hemodynamically significant mitral valve stenosis. Approximately 250 eligible participants, age 18 years or older, with a history of paroxysmal, persistent, or long standing persistent NVAF who are scheduled to undergo an elective catheter ablation procedure will be randomized in a 1:1 ratio to receive either rivaroxaban 20 mg orally, once-daily, administered preferably with the evening meal or VKA (adjusted to achieve a recommended International Normalized Ratio of 2.0 to 3.0).
The study will consist of a screening period, a pre-procedure period, procedure period and post-procedure period. The screening period will begin up to 2 weeks prior to randomization. Participants will be randomized at the beginning of the pre-procedure period. During this period, participants will be recommended to receive their assigned treatment for at least 4 weeks (maximum of 5 weeks) before the catheter ablation procedure. For participants with the sufficient anticoagulation, documented for the 3 weeks prior to randomization, and for participants with a transesophageal echocardiogram (TEE) or intracardiac echocardiography (ICE), the length of the pre-procedure period may be reduced down to 1-7 days and must include any transition from the previous anticoagulation therapy to randomized study drug.
After the catheter ablation procedure, participants will receive their post-procedure dose of study drug through a minimum of 30 + - 5 days. In addition to scheduled visits and telephone calls the study may also include additional phone calls and visits by the participant to the site when dose adjustment is required for usual care.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| rivaroxaban | Experimental | rivaroxaban 20 mg orally, once-daily, administered preferably with the evening meal |
|
| vitamin K antagonist (VKA) | Experimental | dose-adjusted vitamin K antagonist (VKA) to achieve a recommended International Normalized Ratio (INR) of 2.0 to 3.0 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rivaroxaban | Drug | rivaroxaban 20 mg orally, once-daily, administered preferably with the evening meal |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Incidence of Post-Procedure Major Bleeding Events | Post-procedure major bleeding events include Thrombolysis in Myocardial Infarction (TIMI), International Society on Thrombosis and Haemostasis (ISTH) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/life threatening bleeding. | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Composite Endpoint of Myocardial Infarction (MI), Ischemic Stroke, Non-Central Nervous System (Non-CNS) Systemic Embolism and Vascular Death | The composite endpoint include Myocardial Infarction (MI), Ischemic Stroke, Non-Central Nervous System (non-CNS) Systemic Embolism and Vascular Death. | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Scientific Affairs, LLC Clinical Trial | Janssen Scientific Affairs, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beverly Hills | California | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25975659 | Derived | Cappato R, Marchlinski FE, Hohnloser SH, Naccarelli GV, Xiang J, Wilber DJ, Ma CS, Hess S, Wells DS, Juang G, Vijgen J, Hugl BJ, Balasubramaniam R, De Chillou C, Davies DW, Fields LE, Natale A; VENTURE-AF Investigators. Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J. 2015 Jul 21;36(28):1805-11. doi: 10.1093/eurheartj/ehv177. Epub 2015 May 14. |
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248 participants were randomized correctly to study, with an equal number of participants randomized to both treatment arms. The intention to treat (ITT) analysis set includes all participants who were correctly randomized into study. There are 5 screen failures who were not included in ITT analysis set because they were incorrectly randomized.
Participants were randomized at 37 sites in 5 countries.
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| ID | Title | Description |
|---|---|---|
| FG000 | Rivaroxaban | Participants were received Rivaroxaban 20 milligram (mg) orally once-daily administered preferably with the evening meal for 8-10 weeks. |
| FG001 | Vitamin K Antagonist |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| uninterrupted vitamin K antagonist (VKA) | Drug | dose-adjusted vitamin K antagonist (VKA) to achieve a recommended International Normalized Ratio (INR) of 2.0 to 3.0 |
|
| Number of Participants With Myocardial Infarction (MI) | The MI was defined as clinical symptoms consistent with myocardial ischemia and cardiac biomarker elevation greater than the site's upper limit of normal (ULN) or development of new pathological Q waves in at least 2 contiguous leads on the electrocardiogram (ECG) or autopsy confirmation, OR Creatine kinase-muscle and brain subunit [or creatine kinase (CK) in the absence of CK-MB] greater than (>) 3 or 5 or 10 x ULN for samples obtained within 24 hours of the procedure if the baseline values were normal or at least a 50 percent (%) increase over elevated baseline values that were stable or decreasing or development of new pathological Q waves in at least 2 contiguous leads on the electrocardiogram. Symptoms of cardiac ischemia were not required. | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure |
| Number of Participants With Ischemic Stroke | Stroke was defined as a new, sudden, focal neurological deficit resulting from a presumed cerebrovascular cause that was not reversible within 24 hours and not due to a readily identifiable cause such as a tumor or seizure. | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure |
| Number of Participants With Non-Central Nervous System (Non-CNS) Systemic Embolism | The Non-CNS systemic embolism was defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms, (example; trauma, atherosclerosis, instrumentation). | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure |
| Number of Participants With Vascular Death | Any death that was not clearly non-vascular. Examples of vascular death included deaths due to bleeding, Myocardial Infarction (MI), stroke, heart failure and arrhythmias. | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure |
| Los Angeles |
| California |
| United States |
| Sacramento | California | United States |
| San Francisco | California | United States |
| Jacksonville | Florida | United States |
| Maywood | Illinois | United States |
| Kansas City | Kansas | United States |
| Boston | Massachusetts | United States |
| Saint Louis Park | Minnesota | United States |
| Ridgewood | New Jersey | United States |
| Flushing | New York | United States |
| Durham | North Carolina | United States |
| Columbus | Ohio | United States |
| Portland | Oregon | United States |
| Erie | Pennsylvania | United States |
| Hershey | Pennsylvania | United States |
| Philadelphia | Pennsylvania | United States |
| Nashville | Tennessee | United States |
| Austin | Texas | United States |
| Dallas | Texas | United States |
| Tyler | Texas | United States |
| Charlottesville | Virginia | United States |
| Seattle | Washington | United States |
| Tacoma | Washington | United States |
| Aalst | Belgium |
| Antwerp | Belgium |
| Bruges | Belgium |
| Genk | Belgium |
| Hasselt | Belgium |
| Brest | France |
| Montpellier | France |
| Pessac | France |
| Toulouse Cedex 9 N/A | France |
| Vandœuvre-lès-Nancy | France |
| Bad Krozingen | Germany |
| Bad Nauheim | Germany |
| Berlin | Germany |
| Dresden | Germany |
| Jena | Germany |
| Mönchengladbach | Germany |
| Neuwied | Germany |
| Bournemouth | United Kingdom |
| Cottingham | United Kingdom |
| London | United Kingdom |
Participants were received dose-adjusted vitamin K antagonist (VKA) to achieve a recommended International Normalized Ratio (INR) of 2.0 to 3.0 for 8-10 weeks.
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Rivaroxaban | Participants were received Rivaroxaban 20 milligram (mg) orally once-daily administered preferably with the evening meal for 8-10 weeks. |
| BG001 | Vitamin K Antagonist | Participants were received dose-adjusted vitamin K antagonist (VKA) to achieve a recommended International Normalized Ratio (INR) of 2.0 to 3.0 for 8-10 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Race | Number | participants |
| ||||||||||||||||
| Ethnicity | Number | participants |
| ||||||||||||||||
| Body-Mass Index | Mean | Standard Deviation | kg/m^2 |
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| Diastolic Blood Pressure | Mean | Standard Deviation | mmHg |
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| Systolic Blood Pressure | Mean | Standard Deviation | mmHg |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Incidence of Post-Procedure Major Bleeding Events | Post-procedure major bleeding events include Thrombolysis in Myocardial Infarction (TIMI), International Society on Thrombosis and Haemostasis (ISTH) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/life threatening bleeding. | Per-protocol analysis set included all randomized participants who took at least 1 dose of study drug and had undergone the catheter ablation procedure. | Posted | Number | Participants | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure |
|
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Composite Endpoint of Myocardial Infarction (MI), Ischemic Stroke, Non-Central Nervous System (Non-CNS) Systemic Embolism and Vascular Death | The composite endpoint include Myocardial Infarction (MI), Ischemic Stroke, Non-Central Nervous System (non-CNS) Systemic Embolism and Vascular Death. | Per-protocol analysis set included all randomized participants who took at least 1 dose of study drug and had undergone the catheter ablation procedure. | Posted | Number | Participants | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Myocardial Infarction (MI) | The MI was defined as clinical symptoms consistent with myocardial ischemia and cardiac biomarker elevation greater than the site's upper limit of normal (ULN) or development of new pathological Q waves in at least 2 contiguous leads on the electrocardiogram (ECG) or autopsy confirmation, OR Creatine kinase-muscle and brain subunit [or creatine kinase (CK) in the absence of CK-MB] greater than (>) 3 or 5 or 10 x ULN for samples obtained within 24 hours of the procedure if the baseline values were normal or at least a 50 percent (%) increase over elevated baseline values that were stable or decreasing or development of new pathological Q waves in at least 2 contiguous leads on the electrocardiogram. Symptoms of cardiac ischemia were not required. | Per-protocol analysis set included all randomized participants who took at least 1 dose of study drug and had undergone the catheter ablation procedure. | Posted | Number | Participants | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Ischemic Stroke | Stroke was defined as a new, sudden, focal neurological deficit resulting from a presumed cerebrovascular cause that was not reversible within 24 hours and not due to a readily identifiable cause such as a tumor or seizure. | Per-protocol analysis set included all randomized participants who took at least 1 dose of study drug and had undergone the catheter ablation procedure. | Posted | Number | Participants | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Non-Central Nervous System (Non-CNS) Systemic Embolism | The Non-CNS systemic embolism was defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms, (example; trauma, atherosclerosis, instrumentation). | Per-protocol analysis set included all randomized participants who took at least 1 dose of study drug and had undergone the catheter ablation procedure. | Posted | Number | Participants | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Vascular Death | Any death that was not clearly non-vascular. Examples of vascular death included deaths due to bleeding, Myocardial Infarction (MI), stroke, heart failure and arrhythmias. | Per-protocol analysis set included all randomized participants who took at least 1 dose of study drug and had undergone the catheter ablation procedure. | Posted | Number | Participants | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure |
|
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Screening up to Week 8-10
The overall treatment-emergent adverse event (TEAEs), serious adverse events, and adverse events leading to discontinuation are based on 244 participants who were randomized and received at least 1 dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rivaroxaban | Participants were received Rivaroxaban 20 milligram (mg) orally once-daily administered preferably with the evening meal for 8-10 weeks. | 17 | 123 | 26 | 123 | ||
| EG001 | Vitamin K Antagonist | Participants were received dose-adjusted vitamin K antagonist (VKA) to achieve a recommended International Normalized Ratio (INR) of 2.0 to 3.0 for 8-10 weeks. | 20 | 121 | 20 | 121 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Atrial flutter | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Atrial tachycardia | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Pericarditis | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Sinus arrest | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Tachyarrhythmia | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Death | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Puncture site haemorrhage | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Bile duct stenosis | Hepatobiliary disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Excoriation | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Tendon rupture | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Vascular pseudoaneurysm | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Fluid overload | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Atonic seizures | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Loss of consciousness | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Arteriovenous fistula | Vascular disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Director Clinical Development | Janssen Scientific Affairs, LLC | ClinicalTrialDisclosure@its.jnj.com |
| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| D001145 | Arrhythmias, Cardiac |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000069552 | Rivaroxaban |
| ID | Term |
|---|---|
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D009025 | Morpholines |
| D010078 | Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Male |
|
| France |
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| Germany |
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| Great Britain |
|
| United States of America |
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| BLACK |
|
| N/A |
|
| WHITE |
|
| N/A |
|
| NOT HISPANIC/LATINO |
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| GUSTO Severe/Life Threatening Bleeding |
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