Clinical trial NCT02168829: Optimal Anticoagulation for Higher Risk Patients Post-Catheter Ablation for Atrial Fibrillation Trial
Official title: The Optimal Anticoagulation for Enhanced Risk Patients Post-Catheter Ablation for Atrial Fibrillation Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Atrial Fibrillation
Stroke
Keywords: AF ablation
Anticoagulation AF ablation
Stroke prevention
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Bayer
name: Biotronik Canada Inc
First posted: 2014-06-20
Enrollment: 1284
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

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.

Primary outcomes:
measure: Composite of stroke, systemic embolism and covert embolic stroke as detected by cerebral MRI
timeFrame: 3 years
Secondary outcomes:
measure: Clinical, overt stroke
timeFrame: Up to 3 years
measure: Incidence of one or more covert MRI stroke(s) >15 mm
timeFrame: Up to 3 years
measure: Composite of all major and minor bleeding
timeFrame: Up to 3 years
measure: Major bleeding only
timeFrame: Up to 3 years
measure: Minor bleeding only
timeFrame: Up to 3 years
measure: Intracranial hemorrhage
timeFrame: Up to 3 years
measure: Transient ischemic attack
timeFrame: Up to 3 years
measure: All-cause mortality
timeFrame: Up to 3 years
measure: Net clinical benefit based on reduction in stroke/TIA rate compared to major bleeding events.
timeFrame: Up to 3 years
measure: Occurrence of non-primary endpoint MRI changes from baseline to final scan
timeFrame: 3 years
measure: Neuropsychological testing
timeFrame: 3 years
measure: Health economics
timeFrame: 3 years
Other outcomes:
Locations:
city: Canberra
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: Melbourne Health
state: Victoria
city: Nedlands
country: Australia
facility: Heart Rhythm Clinic
state: Western Australia
city: Aalst
country: Belgium
facility: Algemeen Stedelijk Ziekenhuis - campus Aalst
city: Aalst
country: Belgium
facility: Onze Lieve Vrouw Ziekenhuis
city: Antwerp
country: Belgium
facility: ZNA Middelheim
city: Arlon
country: Belgium
facility: Arlon - Clinique du Sud-Luxembourg
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis
city: Brugge
country: Belgium
facility: AZ Sint-Jan (Brugge)
city: Brussels
country: Belgium
facility: Sint-Jean - Kliniek Sint-Jan (Brussels)
city: Brussel
country: Belgium
facility: Europa Ziekenhuizen - ST-ELISABETH
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (UZA)
city: Ghent
country: Belgium
facility: Middelares Gent - AZ Maria Middelares
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Lanaken
country: Belgium
facility: Ziekenhuis Oost-Limburg , campus St Jan
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven, campus Gasthuisberg
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
city: Roeselare
country: Belgium
facility: AZ Delta campus Wilgenstraat
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: New Westminster
country: Canada
facility: Royal Columbian/Fraser Clinical Trials
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Victoria Cardiac Arrhythmia Trials Inc.
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Centre
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Kitchener
country: Canada
facility: St. Mary's General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: Scarborough Health Network- Rougevalley
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Granby
country: Canada
facility: Sherbrooke- Grandby site
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de L'Universite de Montreal (CHUM)
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Montreal
country: Canada
facility: Montreal Health Institute
state: Quebec
city: Montréal
country: Canada
facility: Hôpital du Sacré-Coeur de Montreal
state: Quebec
city: Quebec City
country: Canada
facility: Institut Universitarie de Cardiologie et de Pneumologie de Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Kelowna
country: Canada
facility: Kelowna Interior Health
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital
state: Zhejiang
city: Coburg
country: Germany
facility: Klinikum Coburg
state: Bayern
city: Bad Nauheim
country: Germany
facility: Kerckhoff Klinik
state: Hessen
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW Ruhr-Universitat Bochum
state: Nordrhein-westfalen
city: Bonn
country: Germany
facility: Elektrophysiologie GFO-Kliniken Bonn
state: Nordrhein-westfalen
city: Köln
country: Germany
facility: Herzzentrum der Universitat Koln
state: Nordrhein-westfalen
city: Bad Segeberg
country: Germany
facility: Segeberger Liniken
state: Schleswig-Holstein
city: Lubeck
country: Germany
facility: UKSH Lubeck
state: Schleswig-Holstein
city: Hamburg
country: Germany
facility: Universitares Herzzentrum Hamburg
city: Hamburg
country: Germany
facility: ASklepios
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig
city: Nahariya
country: Israel
facility: Galilee Medical Centre
Study officials:
affiliation: Southlake Regional Health Centre
name: Atul Verma, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Heart Institute Research Corporation
name: David H Birnie, MD
role: PRINCIPAL_INVESTIGATOR
References: