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

• Sponsor: Ottawa Heart Institute Research Corporation (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT02168829
• Collaborator: Canadian Institutes of Health Research (CIHR) (Other), Bayer (Industry), Biotronik Canada Inc (Industry)
• Enrollment: 1,572
• Locations: 55
• Arms: 2
• Duration (Months): 115
• Patients Per Site: 28.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation; Stroke	Drug: Rivaroxaban; Drug: Acetylsalicylic acid	Phase 4

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 1572 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: The Optimal Anticoagulation for Enhanced Risk Patients Post-Catheter Ablation for Atrial Fibrillation Trial
• Study Start Date: Jan 1, 2016
• Anticipated Primary Completion Date: Mar 1, 2025
• Anticipated Study Completion Date: Aug 1, 2025

Arms and Interventions

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: Aspirin ASA

Outcome Measures

Primary Outcome Measures

1. Composite of stroke, systemic embolism and covert embolic stroke as detected by cerebral MRI [3 years]

   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.

Secondary Outcome Measures

1. Clinical, overt stroke [Up to 3 years]

   Clinical, Overt stroke

2. Incidence of one or more covert MRI stroke(s) >15 mm [Up to 3 years]

   Incidence of one or more covert MRI stroke(s) >15 mm

3. Composite of all major and minor bleeding [Up to 3 years]

   Composite of all major and minor bleeding

4. Major bleeding only [Up to 3 years]

   Major bleeding only

5. Minor bleeding only [Up to 3 years]

   Minor bleeding only

6. Intracranial hemorrhage [Up to 3 years]

   Intracranial hemorrhage (clinical and covert on MRI alone)

7. Transient ischemic attack [Up to 3 years]

   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

8. All-cause mortality [Up to 3 years]

   All-cause mortality

9. Net clinical benefit based on reduction in stroke/TIA rate compared to major bleeding events. [Up to 3 years]

   Net clinical benefit based on reduction in stroke/TIA rate compared to major bleeding events.

10. Occurrence of non-primary endpoint MRI changes from baseline to final scan [3 years]

    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

11. Neuropsychological testing [3 years]

    Neuropsychological testing - performed at baseline and repeated at 3 years.

12. Health economics [3 years]

    Cost utilization and cost effectiveness analysis

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. Pregnancy or breastfeeding.

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

3. Patients who are > 85 years of age.

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Canberra Hospital	Canberra	Australian Capital Territory	Australia	2605
2	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
3	The Alfred Melbourne	Melbourne	Victoria	Australia	3004
4	Melbourne Health	Melbourne	Victoria	Australia	3050
5	Heart Rhythm Clinic	Nedlands	Western Australia	Australia	6009
6	Algemeen Stedelijk Ziekenhuis - campus Aalst	Aalst		Belgium
7	Onze Lieve Vrouw Ziekenhuis	Aalst		Belgium
8	ZNA Middelheim	Antwerp		Belgium
9	Arlon - Clinique du Sud-Luxembourg	Arlon		Belgium
10	Imeldaziekenhuis	Bonheiden		Belgium
11	AZ Sint-Jan (Brugge)	Brugge		Belgium
12	Sint-Jean - Kliniek Sint-Jan (Brussels)	Brussels		Belgium
13	Europa Ziekenhuizen - ST-ELISABETH	Brussel		Belgium
14	Universitair Ziekenhuis Antwerpen (UZA)	Edegem		Belgium
15	Middelares Gent - AZ Maria Middelares	Ghent		Belgium
16	Universitair Ziekenhuis Gent	Ghent		Belgium
17	Jessa Ziekenhuis	Hasselt		Belgium
18	Ziekenhuis Oost-Limburg , campus St Jan	Lanaken		Belgium
19	Universitair Ziekenhuis Leuven, campus Gasthuisberg	Leuven		Belgium
20	Centre Hospitalier Universitaire de Liège	Liège		Belgium
21	AZ Delta campus Wilgenstraat	Roeselare		Belgium
22	Foothills Medical Centre	Calgary	Alberta	Canada
23	Royal Columbian/Fraser Clinical Trials	New Westminster	British Columbia	Canada	V3L 3W4
24	St. Paul's Hospital	Vancouver	British Columbia	Canada
25	Victoria Cardiac Arrhythmia Trials Inc.	Victoria	British Columbia	Canada
26	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia	Canada
27	Hamilton Health Sciences Centre	Hamilton	Ontario	Canada
28	Kingston General Hospital	Kingston	Ontario	Canada
29	St. Mary's General Hospital	Kitchener	Ontario	Canada
30	London Health Sciences Centre	London	Ontario	Canada
31	Southlake Regional Health Centre	Newmarket	Ontario	Canada
32	University of Ottawa Heart Institute	Ottawa	Ontario	Canada	K1Y 4W7
33	Scarborough Health Network- Rougevalley	Toronto	Ontario	Canada
34	St. Michael's Hospital	Toronto	Ontario	Canada
35	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada
36	Sherbrooke- Grandby site	Granby	Quebec	Canada
37	Centre Hospitalier de L'Universite de Montreal (CHUM)	Montreal	Quebec	Canada
38	McGill University Health Centre	Montreal	Quebec	Canada
39	Montreal Health Institute	Montreal	Quebec	Canada
40	Hôpital du Sacré-Coeur de Montreal	Montréal	Quebec	Canada
41	Institut Universitarie de Cardiologie et de Pneumologie de Quebec	Quebec City	Quebec	Canada
42	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec	Canada
43	Kelowna Interior Health	Kelowna		Canada
44	Sir Run Run Shaw Hospital	Hangzhou	Zhejiang	China
45	Klinikum Coburg	Coburg	Bayern	Germany	96450
46	Kerckhoff Klinik	Bad Nauheim	Hessen	Germany	61231
47	Herz- und Diabeteszentrum NRW Ruhr-Universitat Bochum	Bad Oeynhausen	Nordrhein-westfalen	Germany	32545
48	Elektrophysiologie GFO-Kliniken Bonn	Bonn	Nordrhein-westfalen	Germany	53225
49	Herzzentrum der Universitat Koln	Köln	Nordrhein-westfalen	Germany	50937
50	Segeberger Liniken	Bad Segeberg	Schleswig-Holstein	Germany	23795
51	UKSH Lubeck	Lubeck	Schleswig-Holstein	Germany	23538
52	Universitares Herzzentrum Hamburg	Hamburg		Germany	20246
53	ASklepios	Hamburg		Germany
54	Herzzentrum Leipzig	Leipzig		Germany	04289
55	Galilee Medical Centre	Nahariya		Israel	22100

Sponsors and Collaborators

• Ottawa Heart Institute Research Corporation
• Canadian Institutes of Health Research (CIHR)
• Bayer
• 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ottawa Heart Institute Research Corporation
• ClinicalTrials.gov Identifier: NCT02168829
• Other Study ID Numbers: 327494
• First Posted: Jun 20, 2014
• Last Update Posted: Mar 25, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Ottawa Heart Institute Research Corporation: AF ablation; Anticoagulation AF ablation; Stroke prevention
• Additional relevant MeSH terms: Atrial Fibrillation; Aspirin; Rivaroxaban

Study Results

No Results Posted as of Mar 25, 2022