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

Stroke Clinical Trial

— OCEAN  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02168829
• Other study ID #: 327494
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: January 2016
• Est. completion date: August 2025

Study information

• Verified date: May 2023
• Source: Ottawa Heart Institute Research Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1284
• Est. completion date: August 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Stroke

Intervention

Drug:
• Rivaroxaban

• Acetylsalicylic acid

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Canberra Hospital	Canberra	Australian Capital Territory
Australia	Melbourne Health	Melbourne	Victoria
Australia	The Alfred Melbourne	Melbourne	Victoria
Australia	Heart Rhythm Clinic	Nedlands	Western Australia
Belgium	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)	Brugge
Belgium	Europa Ziekenhuizen - ST-ELISABETH	Brussel
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
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Sherbrooke- Grandby site	Granby	Quebec
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Hamilton Health Sciences Centre	Hamilton	Ontario
Canada	Kelowna Interior Health	Kelowna
Canada	Kingston General Hospital	Kingston	Ontario
Canada	St. Mary's General Hospital	Kitchener	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Centre Hospitalier de L'Universite de Montreal (CHUM)	Montreal	Quebec
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Montreal Health Institute	Montreal	Quebec
Canada	Hôpital du Sacré-Coeur de Montreal	Montréal	Quebec
Canada	Royal Columbian/Fraser Clinical Trials	New Westminster	British Columbia
Canada	Southlake Regional Health Centre	Newmarket	Ontario
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Institut Universitarie de Cardiologie et de Pneumologie de Quebec	Quebec City	Quebec
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Scarborough Health Network- Rougevalley	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
Canada	Victoria Cardiac Arrhythmia Trials Inc.	Victoria	British Columbia
China	Sir Run Run Shaw Hospital	Hangzhou	Zhejiang
Germany	Kerckhoff Klinik	Bad Nauheim	Hessen
Germany	Herz- und Diabeteszentrum NRW Ruhr-Universitat Bochum	Bad Oeynhausen	Nordrhein-westfalen
Germany	Segeberger Liniken	Bad Segeberg	Schleswig-Holstein
Germany	Elektrophysiologie GFO-Kliniken Bonn	Bonn	Nordrhein-westfalen
Germany	Klinikum Coburg	Coburg	Bayern
Germany	ASklepios	Hamburg
Germany	Universitares Herzzentrum Hamburg	Hamburg
Germany	Herzzentrum der Universitat Koln	Köln	Nordrhein-westfalen
Germany	Herzzentrum Leipzig	Leipzig
Germany	UKSH Lubeck	Lubeck	Schleswig-Holstein
Israel	Galilee Medical Centre	Nahariya

Sponsors (4)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation	Bayer, Biotronik Canada Inc, Canadian Institutes of Health Research (CIHR)

Countries where clinical trial is conducted

Australia,  Belgium,  Canada,  China,  Germany,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Clinical, overt stroke	Clinical, Overt stroke	Up to 3 years
Secondary	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
Secondary	Composite of all major and minor bleeding	Composite of all major and minor bleeding	Up to 3 years
Secondary	Major bleeding only	Major bleeding only	Up to 3 years
Secondary	Minor bleeding only	Minor bleeding only	Up to 3 years
Secondary	Intracranial hemorrhage	Intracranial hemorrhage (clinical and covert on MRI alone)	Up to 3 years
Secondary	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
Secondary	All-cause mortality	All-cause mortality	Up to 3 years
Secondary	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
Secondary	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
Secondary	Neuropsychological testing	Neuropsychological testing - performed at baseline and repeated at 3 years.	3 years
Secondary	Health economics	Cost utilization and cost effectiveness analysis	3 years