A Study Exploring Two Treatment Strategies in Patients With Atrial Fibrillation Who Undergo Catheter Ablation Therapy

A Randomized, Open-label, Active-controlled Multi-center Study to Assess Safety of Uninterrupted Rivaroxaban vs. Usual Care in Subjects Undergoing Catheter Ablation Therapy for Atrial Fibrillation

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01729871

Acronym

VENTURE-AF

Enrollment

253

Registered

2012-11-20

Start date

2013-02-28

Completion date

2014-10-31

Last updated

2017-03-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Atrial Fibrillation

Keywords

Atrial Fibrillation, Irregular heart beat, Catheter Ablation, Rivaroxaban

Brief summary

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.

Detailed description

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.

Interventions

DRUGrivaroxaban

rivaroxaban 20 mg orally, once-daily, administered preferably with the evening meal

DRUGuninterrupted vitamin K antagonist (VKA)

dose-adjusted vitamin K antagonist (VKA) to achieve a recommended International Normalized Ratio (INR) of 2.0 to 3.0

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Be scheduled for a catheter ablation procedure for non-valvular atrial fibrillation (NVAF); * Have a documented history of paroxysmal (lasting \<1 week) or persistent (lasting \>1 week and \<1 year or requiring pharmacological or electrical cardioversion), or long standing persistent (\>=1 year) NVAF; * Be suitable for anticoagulant therapy and catheter ablation as per the judgment of the investigator; * Women must be postmenopausal before entry or practicing a highly effective method of birth control when heterosexually active; * Women of childbearing potential must have a negative serum pregnancy test at screening; * Be willing and able to adhere to the prohibitions and restrictions specified in the study protocol; * Have a life expectancy of at least 6 months

Exclusion criteria

* Has a history of a prior stroke, transient ischemic attack (TIA) or non-convulsive status epilepticus within 6 months of the screening visit; * Has a history of a major bleeding or thromboembolic event within the 12 months immediately preceding the catheter ablation procedure; * Has had major surgery (requiring general anesthesia), within 6 months before screening or planned surgery during the time the subject is expected to participate in the study; * Has NVAF due to electrolyte imbalance, hyperthyroidism, or other reversible or noncardiac cause of NVAF; * Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (eg, compromise the well-being) of the participant or that could prevent, limit, or confound the protocol-specified assessments

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Incidence of Post-Procedure Major Bleeding Events	Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure	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.

Secondary

Measure	Time frame	Description
Number of Participants With Composite Endpoint of 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	The composite endpoint include Myocardial Infarction (MI), Ischemic Stroke, Non-Central Nervous System (non-CNS) Systemic Embolism and Vascular Death.
Number of Participants With Myocardial Infarction (MI)	Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure	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.
Number of Participants With Ischemic Stroke	Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure	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.
Number of Participants With Non-Central Nervous System (Non-CNS) Systemic Embolism	Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure	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).
Number of Participants With Vascular Death	Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure	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.

Countries

Belgium, France, Germany, United Kingdom, United States

Participant flow

Recruitment details

Participants were randomized at 37 sites in 5 countries.

Pre-assignment details

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 by arm

Arm	Count
Rivaroxaban Participants were received Rivaroxaban 20 milligram (mg) orally once-daily administered preferably with the evening meal for 8-10 weeks.	124
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.	124
Total	248

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	7	7
Overall Study	Death	0	1
Overall Study	Lack of Efficacy	0	1
Overall Study	Other	4	9
Overall Study	Physician Decision	0	2
Overall Study	Protocol Violation	1	0
Overall Study	Withdrawal by Subject	0	3

Baseline characteristics

Characteristic	Rivaroxaban	Vitamin K Antagonist	Total
Age, Continuous	58.6 years STANDARD_DEVIATION 9.86	60.5 years STANDARD_DEVIATION 10.51	59.5 years STANDARD_DEVIATION 10.21
Body-Mass Index	29.8 kg/m^2 STANDARD_DEVIATION 5.74	28.9 kg/m^2 STANDARD_DEVIATION 5.49	29.4 kg/m^2 STANDARD_DEVIATION 5.62
Diastolic Blood Pressure	81 mmHg STANDARD_DEVIATION 9.85	79.4 mmHg STANDARD_DEVIATION 10.78	80.2 mmHg STANDARD_DEVIATION 10.34
Ethnicity HISPANIC/LATINO	0 participants	4 participants	4 participants
Ethnicity N/A	34 participants	26 participants	60 participants
Ethnicity NOT HISPANIC/LATINO	90 participants	94 participants	184 participants
Race ASIAN	5 participants	2 participants	7 participants
Race BLACK	3 participants	3 participants	6 participants
Race N/A	4 participants	3 participants	7 participants
Race WHITE	112 participants	116 participants	228 participants
Region of Enrollment Belgium	24 participants	24 participants	48 participants
Region of Enrollment France	19 participants	19 participants	38 participants
Region of Enrollment Germany	18 participants	19 participants	37 participants
Region of Enrollment Great Britain	24 participants	24 participants	48 participants
Region of Enrollment United States of America	39 participants	38 participants	77 participants
Sex: Female, Male Female	38 Participants	34 Participants	72 Participants
Sex: Female, Male Male	86 Participants	90 Participants	176 Participants
Systolic Blood Pressure	133.3 mmHg STANDARD_DEVIATION 15.6	131.2 mmHg STANDARD_DEVIATION 17.68	132.2 mmHg STANDARD_DEVIATION 16.67

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	26 / 123	20 / 121
serious Total, serious adverse events	17 / 123	20 / 121

Outcome results

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.

Time frame: Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure