Optimal Anticoagulation for Higher Risk Patients Post-Catheter Ablation for Atrial Fibrillation Trial

NCT ID: NCT02168829

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1284 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2025-08-14

Brief Summary

This trial is comparing medical approaches for stroke prevention in people who have atrial fibrillation (AF) and have undergone a successful procedure called ablation to eliminate or substantially reduce the arrhythmia. AF is normally associated with an increased risk of stroke which in many patients can be prevented with appropriate blood thinner therapy. This trial will compare a strategy of oral anticoagulant therapy after successful ablation to therapy with an aspirin per day.

Detailed Description

This is a prospective, open-label, randomized trial to investigate whether a strategy of ongoing, long-term oral anticoagulation with rivaroxaban 15 mg daily is superior to a strategy of antiplatelet therapy, ASA 75-160 mg, alone in preventing cerebral embolic events in moderately high risk patients following successful catheter ablation for atrial fibrillation..

At least one year post-successful catheter ablation for AF or left atrial flutter/tachycardia without evidence of any clinically apparent arrhythmia recurrence based on at least one 24 hour Holter and ECG within 6 months after the last ablation procedure and at least one 24 hour Holter and ECG between 6 and 12 months post-ablation or beyond. Patient must have no atrial fibrillation, atrial flutter or atrial tachycardia > 30 seconds detected on a minimum 48 hour Holter monitor within two months prior to enrollment.

Patients will be randomized in a 1:1 fashion to ASA 75-160 mg daily or rivaroxaban 15 mg daily. Patients will be seen at 6 months, one year and every year thereafter for a minimum of 3 years. Blood chemistry tests, ECG, holters and patient quality of life questionnaires will be done annually.

Cerebral MRI scanning at baseline and at three years will be done for assessment of silent cerebral infarction. MRI imaging will be performed using a specific protocol.

A pre-specified subset of patients will undergo insertion of a implantable loop recorder (ILR) capable of automated AF detection.

Conditions

Atrial Fibrillation; Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Rivaroxaban

Rivaroxaban 15 mg daily

Group Type: ACTIVE_COMPARATOR

Rivaroxaban

Intervention Type: DRUG

Acetylsalicylic acid (ASA)

ASA 75-160 mg daily (if intolerant to ASA, no antiplatelet therapy will be prescribed)

Group Type: ACTIVE_COMPARATOR

Acetylsalicylic acid

Intervention Type: DRUG

Interventions

Rivaroxaban

Intervention Type: DRUG

Acetylsalicylic acid

Intervention Type: DRUG

Other Intervention Names

Xarelto; Aspirin; ASA

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.

3. Patient must be >18 years of age.

4. Patient must have non-valvular AF.

2. Patient is unable or unwilling to provide informed consent.

3. Patient is included in another randomized clinical trial or a clinical trial requiring an insurance.

4. Patient has been on an investigational drug within 30 days of enrolment.

5. 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.

6. Patient has creatinine clearance < 30 mL/min.

7. 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).

8. Patient has other contraindication to oral anticoagulation or treatment with antiplatelet agent (such as allergy).

9. Patient has a contraindication to magnetic resonance imaging (MRI) or is unlikely to tolerate due to severe claustrophobia.

10. Patients with a contraindication to implantation of an implantable loop recorder if the patient opts for a loop recorder as part of the study (such as limited immunocompetence or a wound healing disorder).

11. Patient has valvular atrial fibrillation [reference AHA guidelines].

12. Patient has a non-arrhythmic condition necessitating long-term oral anticoagulation.

13. Patient had a severe, disabling stroke within one year prior to enrollment or any stroke within 14 days of enrollment.

14. 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.

15. Pregnancy or breastfeeding.

16. Women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study.

17. Patients who are > 85 years of age.

18. Patients who are critically ill or who have a life expectancy <3 years.

19. Patients for whom the investigator believes that the trial is not in the interest of the patient.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: collaborator

Biotronik Canada Inc

INDUSTRY

Sponsor Role: collaborator

Abbott

INDUSTRY

Sponsor Role: collaborator

Ottawa Heart Institute Research Corporation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Atul Verma, MD

Role: PRINCIPAL_INVESTIGATOR

Southlake Regional Health Centre

David H Birnie, MD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Heart Institute Research Corporation

Locations

Canberra Hospital

Canberra, Australian Capital Territory, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

The Alfred Melbourne

Melbourne, Victoria, Australia

Melbourne Health

Melbourne, Victoria, Australia

Heart Rhythm Clinic

Nedlands, Western Australia, Australia

Algemeen Stedelijk Ziekenhuis - campus Aalst

Aalst, , Belgium

Onze Lieve Vrouw Ziekenhuis

Aalst, , Belgium

ZNA Middelheim

Antwerp, , Belgium

Arlon - Clinique du Sud-Luxembourg

Arlon, , Belgium

Imeldaziekenhuis

Bonheiden, , Belgium

AZ Sint-Jan (Brugge)

Bruges, , Belgium

Europa Ziekenhuizen - ST-ELISABETH

Brussels, , Belgium

Sint-Jean - Kliniek Sint-Jan (Brussels)

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen (UZA)

Edegem, , Belgium

Middelares Gent - AZ Maria Middelares

Ghent, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Jessa Ziekenhuis

Hasselt, , Belgium

Ziekenhuis Oost-Limburg , campus St Jan

Lanaken, , Belgium

Universitair Ziekenhuis Leuven, campus Gasthuisberg

Leuven, , Belgium

Centre Hospitalier Universitaire de Liège

Liège, , Belgium

AZ Delta campus Wilgenstraat

Roeselare, , Belgium

Foothills Medical Centre

Calgary, Alberta, Canada

Royal Columbian/Fraser Clinical Trials

New Westminster, British Columbia, Canada

St. Paul's Hospital

Vancouver, British Columbia, Canada

Victoria Cardiac Arrhythmia Trials Inc.

Victoria, British Columbia, Canada

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Hamilton Health Sciences Centre

Hamilton, Ontario, Canada

Kingston General Hospital

Kingston, Ontario, Canada

St. Mary's General Hospital

Kitchener, Ontario, Canada

London Health Sciences Centre

London, Ontario, Canada

Southlake Regional Health Centre

Newmarket, Ontario, Canada

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Scarborough Health Network- Rougevalley

Toronto, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Sherbrooke- Grandby site

Granby, Quebec, Canada

Centre Hospitalier de L'Universite de Montreal (CHUM)

Montreal, Quebec, Canada

Hôpital du Sacré-Coeur de Montreal

Montreal, Quebec, Canada

McGill University Health Centre

Montreal, Quebec, Canada

Montreal Health Institute

Montreal, Quebec, Canada

Institut Universitarie de Cardiologie et de Pneumologie de Quebec

Québec, Quebec, Canada

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Kelowna Interior Health

Kelowna, , Canada

Sir Run Run Shaw Hospital

Hangzhou, Zhejiang, China

Klinikum Coburg

Coburg, Bavaria, Germany

Kerckhoff Klinik

Bad Nauheim, Hesse, Germany

Herzzentrum Leipzig

Leipzig, Leipzig, Germany

Herz- und Diabeteszentrum NRW Ruhr-Universitat Bochum

Bad Oeynhausen, North Rhine-Westphalia, Germany

Elektrophysiologie GFO-Kliniken Bonn

Bonn, North Rhine-Westphalia, Germany

Herzzentrum der Universitat Koln

Cologne, North Rhine-Westphalia, Germany

Segeberger Liniken

Bad Segeberg, Schleswig-Holstein, Germany

UKSH Lubeck

Lübeck, Schleswig-Holstein, Germany

Universitares Herzzentrum Hamburg

Hamburg, , Germany

ASklepios

Hamburg, , Germany

Galilee Medical Centre

Nahariya, , Israel

Countries

Australia; Belgium; Canada; China; Germany; Israel

Other Identifiers

327494

Identifier Type: -

Identifier Source: org_study_id