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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Stroke; Atrial Fibrillation
• Intervention / Treatment: Drug: Rivaroxaban; Drug: Acetylsalicylic acid

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.

• Study Type: Interventional
• Enrollment (Actual): 1284
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sonya Jancar, RN,CRA,CCRP; Phone Number: 19678 613-696-7000; Email: ocean@ottawaheart.ca

Study Locations

• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia, 2605
      • Canberra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3050
      • Melbourne Health
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Melbourne
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Heart Rhythm Clinic
• Belgium
  • Aalst, Belgium
    • Onze Lieve Vrouw Ziekenhuis
  • Aalst, Belgium
    • Algemeen Stedelijk Ziekenhuis - campus Aalst
  • Antwerp, Belgium
    • ZNA Middelheim
  • Arlon, Belgium
    • Arlon - Clinique du Sud-Luxembourg
  • Bonheiden, Belgium
    • Imeldaziekenhuis
  • Brugge, Belgium
    • AZ Sint-Jan (Brugge)
  • Brussel, Belgium
    • Europa Ziekenhuizen - ST-ELISABETH
  • Brussels, Belgium
    • Sint-Jean - Kliniek Sint-Jan (Brussels)
  • Edegem, Belgium
    • Universitair Ziekenhuis Antwerpen (UZA)
  • Ghent, Belgium
    • Universitair Ziekenhuis Gent
  • Ghent, Belgium
    • Middelares Gent - AZ Maria Middelares
  • Hasselt, Belgium
    • Jessa Ziekenhuis
  • Lanaken, Belgium
    • Ziekenhuis Oost-Limburg , campus St Jan
  • Leuven, Belgium
    • Universitair Ziekenhuis Leuven, Campus Gasthuisberg
  • Liège, Belgium
    • Centre Hospitalier Universitaire de Liège
  • Roeselare, Belgium
    • AZ Delta Campus Wilgenstraat
• Canada
  • Kelowna, Canada
    • Kelowna Interior Health
  • Alberta
    • Calgary, Alberta, Canada
      • Foothills Medical Centre
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W4
      • Royal Columbian/Fraser Clinical Trials
    • Vancouver, British Columbia, Canada
      • St. Paul's Hospital
    • Victoria, British Columbia, Canada
      • Victoria Cardiac Arrhythmia Trials Inc.
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • Queen Elizabeth II Health Sciences Centre
  • Ontario
    • Hamilton, Ontario, Canada
      • Hamilton Health Sciences Centre
    • Kingston, Ontario, Canada
      • Kingston General Hospital
    • Kitchener, Ontario, Canada
      • St. Mary's General Hospital
    • London, Ontario, Canada
      • London Health Sciences Centre
    • Newmarket, Ontario, Canada
      • Southlake Regional Health Centre
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
    • Toronto, Ontario, Canada
      • St. Michael's Hospital
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada
      • Scarborough Health Network- Rougevalley
  • Quebec
    • Granby, Quebec, Canada
      • Sherbrooke- Grandby site
    • Montreal, Quebec, Canada
      • McGill University Health Centre
    • Montreal, Quebec, Canada
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
    • Montreal, Quebec, Canada
      • Montreal Health Institute
    • Montréal, Quebec, Canada
      • Hopital du Sacre-Coeur de Montreal
    • Quebec City, Quebec, Canada
      • Institut Universitarie de Cardiologie et de Pneumologie de Quebec
    • Sherbrooke, Quebec, Canada
      • Centre Hospitalier Universitaire de Sherbrooke
• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Sir Run Run Shaw Hospital
• Germany
  • Hamburg, Germany, 20246
    • Universitares Herzzentrum Hamburg
  • Hamburg, Germany
    • ASklepios
  • Leipzig, Germany, 04289
    • Herzzentrum Leipzig
  • Bayern
    • Coburg, Bayern, Germany, 96450
      • Klinikum Coburg
  • Hessen
    • Bad Nauheim, Hessen, Germany, 61231
      • Kerckhoff Klinik
  • Nordrhein-westfalen
    • Bad Oeynhausen, Nordrhein-westfalen, Germany, 32545
      • Herz- und Diabeteszentrum NRW Ruhr-Universitat Bochum
    • Bonn, Nordrhein-westfalen, Germany, 53225
      • Elektrophysiologie GFO-Kliniken Bonn
    • Köln, Nordrhein-westfalen, Germany, 50937
      • Herzzentrum der Universitat Koln
  • Schleswig-Holstein
    • Bad Segeberg, Schleswig-Holstein, Germany, 23795
      • Segeberger Liniken
    • Lubeck, Schleswig-Holstein, Germany, 23538
      • UKSH Lübeck
• Israel
  • Nahariya, Israel, 22100
    • Galilee Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Exclusion Criteria

1. Patient does not meet all of the above listed inclusion criteria.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rivaroxaban; Rivaroxaban 15 mg daily	Drug: Rivaroxaban; Other Names: Xarelto
Active Comparator: Acetylsalicylic acid (ASA); ASA 75-160 mg daily (if intolerant to ASA, no antiplatelet therapy will be prescribed)	Drug: Acetylsalicylic acid; Other Names: ASA; Aspirin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of stroke, systemic embolism and covert embolic stroke as detected by cerebral MRI	Composite of stroke, systemic embolism and covert embolic stroke as detected by cerebral MRI. A patient will be considered to have a covert stroke if one or more lesions > 15 mm has been detected between the baseline, and final (3 year) MRI on T2 weighted and/or FLAIR imaging protocols.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical, overt stroke	Clinical, Overt stroke	Up to 3 years
Incidence of one or more covert MRI stroke(s) >15 mm	Incidence of one or more covert MRI stroke(s) >15 mm	Up to 3 years
Composite of all major and minor bleeding	Composite of all major and minor bleeding	Up to 3 years
Major bleeding only	Major bleeding only	Up to 3 years
Minor bleeding only	Minor bleeding only	Up to 3 years
Intracranial hemorrhage	Intracranial hemorrhage (clinical and covert on MRI alone)	Up to 3 years
Transient ischemic attack	Transient ischemic attack defined as presence of a new focal neurologic deficit thought to be vascular in origin, with signs or symptoms lasting <24 hours	Up to 3 years
All-cause mortality	All-cause mortality	Up to 3 years
Net clinical benefit based on reduction in stroke/TIA rate compared to major bleeding events.	Net clinical benefit based on reduction in stroke/TIA rate compared to major bleeding events.	Up to 3 years
Occurrence of non-primary endpoint MRI changes from baseline to final scan	Occurrence of non-primary endpoint MRI changes from baseline to final scan including: quantification of cerebral atrophy, quantification of cerebral white matter changes, number of all new MRI lesions > 3mm, >5 mm, > 15 mm, and > 20 mm, and number of lesions detected exclusively on DW-MRI	3 years
Neuropsychological testing	Neuropsychological testing - performed at baseline and repeated at 3 years.	3 years
Health economics	Cost utilization and cost effectiveness analysis	3 years

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation
• Collaborators: Bayer; Canadian Institutes of Health Research (CIHR); Biotronik Canada Inc
• Investigators: Principal Investigator: Atul Verma, MD, Southlake Regional Health Centre; Principal Investigator: David H Birnie, MD, Ottawa Heart Institute Research Corporation

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): July 1, 2025
• Study Completion (Anticipated): August 1, 2025

Study Registration Dates

• First Submitted: June 18, 2014
• First Submitted That Met QC Criteria: June 18, 2014
• First Posted (Estimate): June 20, 2014

Study Record Updates

• Last Update Posted (Actual): May 19, 2023
• Last Update Submitted That Met QC Criteria: May 18, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Stroke prevention; AF ablation; Anticoagulation AF ablation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Aspirin; Rivaroxaban
• Other Study ID Numbers: 327494

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED