Evaluation of Long-term Oral Anticoagulation with Rivaroxaban Versus Acetylsalicylic Acid in Moderate Risk Post-Catheter Ablation Atrial Fibrillation Patients

Trial ID: 2024-518736-37-00
Protocol: OHIRC-20150866
Sponsor: University Of Ottawa Heart Institute

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Diseases & Conditions

Atrial fibrillation Embolic stroke Cardiac ablation

Objectives

The primary objective of this phase 4 trial is to determine whether a strategy of ongoing, long-term oral **anticoagulation** is superior to a strategy of antiplatelet therapy (ASA) alone in reducing the incidence of cerebral embolic events in moderate-risk patients post-successful catheter ablation for **atrial fibrillation**. This is clinically relevant as it addresses the optimal management strategy to prevent stroke in this patient population, potentially improving outcomes and reducing the risk of embolic events.

Secondary objectives include:

Evaluation of the efficacy of **rivaroxaban** and ASA, respectively, in reducing the incidence of stroke, systemic embolism, or silent cerebral infarction.
Assessment of the safety of long-term oral anticoagulation after catheter ablation for atrial fibrillation.
Evaluation of the cost-effectiveness of long-term oral anticoagulation after catheter ablation for atrial fibrillation.
Investigation of the relationship between the atrial fibrillation burden and stroke risk.

Participants

The clinical trial involves a total of **1002 participants** who are at risk of stroke due to **Atrial Fibrillation**. The study population includes both male and female subjects, aged 18 years and older, who have undergone successful catheter ablation for atrial fibrillation and are at moderate risk of cerebral embolic events. Participants were selected based on specific criteria, including being at least one year post-ablation without evidence of arrhythmia recurrence and having a CHA2DS2-VASc risk score of 1 or more, excluding those whose sole risk factor is female sex or vascular disease. The trial includes a vulnerable population, and participants are required to have non-valvular atrial fibrillation. Lifestyle factors such as diet and physical activity were not specified in the data provided.

Plans and Procedures

This clinical trial is a **randomized**, **double-blind**, controlled study designed to evaluate the efficacy of long-term oral anticoagulation compared to antiplatelet therapy in reducing cerebral embolic events in patients at moderate risk following successful catheter ablation for **atrial fibrillation**. The trial involves two groups: one receiving **rivaroxaban** and the other receiving **acetylsalicylic acid**. The study is expected to last until July 31, 2025, with participant involvement spanning up to 36 months. The trial's primary endpoint is a composite of stroke, systemic embolism, and covert embolic stroke, assessed via cerebral magnetic resonance imaging. Secondary endpoints include clinical stroke, incidence of covert MRI strokes, bleeding events, transient ischemic attacks, and overall mortality, among others.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as being at least one year post-successful catheter ablation without arrhythmia recurrence and having a CHA2DS2-VASc score of 1 or more. Follow-up visits will occur at regular intervals to monitor health status, medication adherence, and any adverse events. The end-of-study visit will include a final assessment of the primary and secondary endpoints. Participants may be withdrawn from the study early if they experience significant adverse effects, non-compliance with the study protocol, or if they choose to withdraw consent.

Treatment

The clinical trial involves the administration of two pharmaceutical products, each with distinct roles in the study. The first product, **ASS-ratiopharm® 100 mg TAH Tabletten**, contains the active substance **acetylsalicylic acid**. This medication is presented in tablet form and is administered orally. The maximum daily dose is 160 mg, with a total treatment period of up to 36 months. The product is manufactured by Ratiopharm GmbH and is utilized as a comparator in the trial. The chemical origin of the active substance is confirmed, and the product is not a pediatric formulation.

The second product, **Xarelto 15 mg film-coated tablets**, contains the active substance **rivaroxaban**. This medication is also administered orally in the form of film-coated tablets. The maximum daily dose is 15 mg, with a treatment duration of up to 36 months. Xarelto is produced by Bayer AG and serves as the test product in the trial. Similar to the comparator, the active substance is of chemical origin, and the formulation is not intended for pediatric use.

Both medications are administered orally, and participant compliance is monitored throughout the study to ensure adherence to the dosing schedule. The trial aims to evaluate the efficacy of long-term oral anticoagulation compared to antiplatelet therapy in reducing cerebral embolic events in patients post-catheter ablation for atrial fibrillation. No additional non-experimental treatments, such as placebo or standard-of-care therapy, are specified in the trial protocol.

Efficacy

Efficacy in the clinical trial titled "The Optimal Anticoagulation for Enhanced Risk Patients Post-Catheter Ablation for Atrial Fibrillation Trial" will be assessed using a combination of primary and secondary endpoints. The primary endpoint is a composite measure that includes **stroke**, systemic embolism, and covert embolic stroke, which will be evaluated through cerebral magnetic resonance imaging (MRI). Secondary endpoints encompass a range of clinical outcomes, including clinical overt stroke, incidence of covert MRI strokes greater than 15 mm, and a composite of all major and minor bleeding events. Additional secondary endpoints include major bleeding, minor bleeding, intracranial hemorrhage, transient ischemic attack, all-cause mortality, and net clinical benefit based on the reduction in stroke or transient ischemic attack rate compared to major bleeding events. The trial will also assess the occurrence of non-primary endpoint MRI changes from baseline to the final scan, neuropsychological testing, quality of life, and cost utilization and cost-effectiveness analysis.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Patient must be at least one year post-successful catheter ablation(s) for atrial fibrillation without evidence of any clinically apparent arrhythmia recurrence defined as all of the following: No AF/AT/AFL on at least 24 hour Holter and an ECG (or equivalent) from 2-6 months after the last ablation, AND no AF/AT/AFL on at least 24 hour Holter and an ECG any time after 6 months after the last ablation AND no AF/AT/AFL on at least 24 hour Holter and ECG 2 months before enrolment in the study. The Holter/ECG within 2 months of enrolment may also serve as the Holter performed 6 months or later after the last ablation - see section 2.3.1 for details
Patient must have a CHA2DS2-VASc risk score of 1 or more. Patients in whom female sex or vascular disease are their sole risk factor may not be enrolled.
Patient must be >18 years of age.
Patient must have non-valvular AF.

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Exclusion Criteria

Patient does not meet all of the above listed inclusion criteria.
Patient is unable or unwilling to provide informed consent.
Patient is included in another randomized clinical trial or a clinical trial requiring an insurance.
Patient has been on an investigational drug within 30 days of enrolment.
Patient has been on strong CYP3A inducers (such as rifampicin, phenytoin, phenobarbital, or carbamazepine) or strong CYP3A inhibitors (such as ketoconazole or protease inhibitors) within 4 days of enrolment.
Patient has creatinine clearance < 30 mL/min.
Patient has bleeding contra-indication to oral anticoagulation (such as bleeding diathesis, hemorrhagic disorder, significant gastrointestinal bleeding within 6 months, intracranial/intraocular/ atraumatic bleeding history, fibrinolysis within 48 hours of enrollment).
Patient has other contraindication to oral anticoagulation or treatment with antiplatelet agent (such as allergy).
Patient has a contraindication to magnetic resonance imaging (MRI) or is unlikely to tolerate due to severe claustrophobia.
Patients with a contraindication to implantation of an implantable loop recorder if the patient opts for loop recorder as part of the study (such as limited immunocompetence or a wound healing disorder).
Patient has valvular atrial fibrillation [reference AHA guidelines].
Patient has a non-arrhythmic condition necessitating long-term oral anticoagulation.
Patient had a severe, disabling stroke within one year prior to enrollment or any stroke within 14 days of enrollment.
Patient with special risk factors for stroke unrelated to AF, specifically known thrombophilia/ hypercoagulability, uncontrolled hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg within 4 days of enrollment), untreated familial hyperlipidemia, known vascular anomaly (intracranial aneurysm/ arteriovenous malformation or chronic vascular dissection), or known severe carotid disease.
Pregnancy or breastfeeding.
Women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study.
Patients who are > 85 years of age.
Patients who are critically ill or who have a life expectancy <3 years.
Patients for whom the investigator believes that the trial is not in the interest of the patient.