Safety of Rivaroxaban in patients with nonvalvular atrial fibrillation who undergo catheter ablatio

Phase 1

• Conditions: Prevention of stroke and non-CNS systemic embolism in patients with nonvalvular atrial fibrillation who undergo catheter ablation; MedDRA version: 14.1 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2012-001484-79-GB
• Lead Sponsor: Janssen-Cilag International NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-10-17
• Study Completion: 2014-10-29
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 248

Inclusion Criteria

• Have a documented history of paroxysmal (lasting <1 week), persistent (lasting >1 week and <1 year or requiring pharmacological or electrical cardioversion), or long standing persistent (= 1 year) NVAF.
• Be scheduled for a first catheter ablation procedure for NVAF.
• Be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
• Be suitable for anticoagulant therapy and catheter ablation as per the judgement of the investigator.
• Be a man or woman 18 years of age, or older.
• If a woman, before entry she must be:
- Postmenopausal, defined as
a. >45 years of age with amenorrhoea for at least 18 months
- Menstrual
a. Surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation or otherwise be incapable of pregnancy) or
b. If heterosexually active, practising a highly effective method of birth control, including hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (eg, condoms, diaphragm or cervical cap with spermicidal foam, cream or gel) or male partner sterilisation, consistent with local regulations regarding use of birth
control methods for subjects participating in clinical trials, for the duration of their participation in the study, or
c. Not heterosexually active, Note: Women who are not heterosexually active at screening must agree to utilise a highly effective method of birth control if they become heterosexually active during their participation in the study. Women must agree to continue using these methods of contraception throughout the
study.
• If a woman of childbearing potential, she must have a negative serum pregnancy test at screening.
• Have a life expectancy of at least 6 months.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 147
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 103

Exclusion Criteria

• Has contraindications to the use of any anticoagulant therapy (eg, bleeding diathesis, history of gastrointestinal bleeding within 1 year or coagulopathy or a platelet count <90,000/µL documented at screening).
• Has a history of a major bleeding or thromboembolic event within the 12 months immediately preceding the catheter ablation procedure.
• Has a history of a prior stroke, TIA or non-convulsive status epilepticus within 6 months of the screening visit.
• Has a CrCl = 50 mL/min at screening
• Has moderate to severe hepatic impairment (Child-Pugh B and C).
• Has a comorbid condition such as severe pulmonary disease, infection, etc., and a life expectancy of less than 6 months.
• Has had major surgery, (eg, requiring general anaesthesia) within 6 months before screening, or will not have fully recovered from surgery, or planned surgery during the time the subject is expected to participate in the study.
Note: subjects with planned surgical procedures to be conducted under local anaesthesia may participate.
• Has a history of cardiac valvular disease, condition, or procedure that does not meet the NVAF definition (the presence of atrial fibrillation 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, or rheumatic heart disease).
• Has NVAF due to electrolyte imbalance, hyperthyroidism or other reversible or noncardiac cause of NVAF.
• Has a left atrial size >55 mm or a documented left atrial thrombus or myxoma on imaging (e.g. echocardiography; the decision about whether or not to have an imaging study prior to the catheter ablation procedure will be made by the principal investigator as per standard of care).
• Has a cardiac ejection fraction =40%, New York Heart Association Class III or IV, or presence of an implantable cardiac defibrillator.
• Has had an MI within the 2 months immediately preceding the catheter ablation procedure or coronary artery bypass graft (CABG) surgery within 6 months immediately preceding the catheter ablation procedure.
• Has known allergies, hypersensitivity, or intolerance to any component of rivaroxaban or VKA or its excipients
• Is receiving treatment for HIV infection (due to potential drug-drug interactions).
• Has a diagnosis or clinical condition requiring use of dual or single anti-platelet therapy (i.e. ASA [any dose] with a thienopyridine or P2Y12 platelet inhibitor, a thienopyridine or P2Y12 platelet inhibitor alone or ASA [>100 mg per day that cannot be decreased to <100 mg at randomisation]).
• Has a history of malignancy within 1 year before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence).
• Uses or receives any of the disallowed therapies before the planned first dose of study drug.
• Has received an investigational drug (including investigational vaccines) or used an invasive investigational medical

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to evaluate the safety of rivaroxaban and uninterrupted vitamin K antagonist (VKA) in adult subjects with nonvalvular atrial fibrillation (NVAF) who undergo catheter ablation as measured by post-procedure major bleeding events.;Secondary Objective: The secondary objective is to evaluate the thromboembolism profile of rivaroxaban and uninterrupted VKA as measured by the composite and the individual components of the following post procedure events: myocardial infarction (MI), ischemic stroke, non-CNS systemic embolism, and vascular death.;Primary end point(s): The primary endpoint for this study is the incidence of post-procedure major bleeding events observed within the first 30 ± 5 days after the catheter ablation procedure;Timepoint(s) of evaluation of this end point: From catheter ablation procedure to End of Treatment (30 ± 5 days)

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): The secondary endpoints for this study include:<br> •Event rate, for the 30 ± 5 days after the catheter ablation procedure, of the secondary composite endpoint of MI, ischemic stroke, non-CNS systemic embolism and vascular death.<br> •Event rate, for the 30 ± 5 days after the catheter ablation procedure, of the individual components of the secondary composite endpoint of MI, ischemic stroke, non-CNS systemic embolism and vascular death.<br> ;Timepoint(s) of evaluation of this end point: From catheter ablation procedure to End of Treatment (30 ± 5 days)