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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Ottawa Heart Institute

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

12 Jan 2018 → 14 Aug 2025

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Canadian Institute for Health Research Canada · Bayer Inc. Canada · Biotronik Inc. Canada

External identifiers

EU CT number

2024-518736-37-00

EudraCT number

2016-002353-38

ClinicalTrials.gov

NCT02168829

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

This phase 4 trial investigates whether a strategy of ongoing, long-term oral anticoagulation is superior to a strategy of antiplatelet therapy (ASA) alone in reducing the incidence of cerebral embolic events in moderate risk patients post-successful catheter ablation for atrial fibrillation.

Secondary objectives 4

1. Evaluation of efficacy of rivaroxaban and ASA, respectively, in the reduction of the incidence of stroke, systemic embolism or silent cerebral infarction
2. Evaluation of safety of long-term oral anticoagulation after catheter ablation for atrial fibrillation
3. Evaluation of cost effectiveness of long-term oral anticoagulation after catheter ablation for atrial fibrillation
4. Evaluation of relationship of the atrial fibrillation burden to stroke risk

Conditions and MedDRA coding

Risk of stroke by Atrial Fibrillation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 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. 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. 3. Patient must be >18 years of age.
4. 4. Patient must have non-valvular AF.

Exclusion criteria 19

1. 1. Patient does not meet all of the above listed inclusion criteria.
2. 2. Patient is unable or unwilling to provide informed consent.
3. 3. Patient is included in another randomized clinical trial or a clinical trial requiring an insurance.
4. 4. Patient has been on an investigational drug within 30 days of enrolment.
5. 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. 6. Patient has creatinine clearance < 30 mL/min.
7. 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. 8. Patient has other contraindication to oral anticoagulation or treatment with antiplatelet agent (such as allergy).
9. 9. Patient has a contraindication to magnetic resonance imaging (MRI) or is unlikely to tolerate due to severe claustrophobia.
10. 10. Patients with a contraindication to implantation of an implantable loop recorder if the patient opts for loop recorder as part of the study (such as limited immunocompetence or a wound healing disorder).
11. 11. Patient has valvular atrial fibrillation [reference AHA guidelines].
12. 12. Patient has a non-arrhythmic condition necessitating long-term oral anticoagulation.
13. 13. Patient had a severe, disabling stroke within one year prior to enrollment or any stroke within 14 days of enrollment.
14. 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. 15. Pregnancy or breastfeeding.
16. 16. Women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study.
17. 17. Patients who are > 85 years of age.
18. 18. Patients who are critically ill or who have a life expectancy <3 years.
19. 19. Patients for whom the investigator believes that the trial is not in the interest of the patient.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome is a composite of stroke, systemic embolism, and covert embolic stroke as defined by assessment of cerebral magnetic resonance imaging.

Secondary endpoints 13

1. 1. Clinical, overt stroke
2. 2. Incidence of one or more covert MRI stroke(s) > 15 mm
3. 3. Composite of all major and minor bleeding
4. 4. Major bleeding only
5. 5. Minor bleeding only
6. 6. Intracranial hemorrhage
7. 7. Transient ischemic attack
8. 8. All-cause mortality
9. 9. Net clinical benefit based on reduction in stroke/TIA rate compared to major bleeding events
10. 10. Occurrence of non-primary endpoint MRI changes from baseline to final scan
11. 11. Neuropsychological testing
12. 12. Quality of life assessment
13. 13. Cost utilization and cost effectiveness analysis

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Ottawa Heart Institute

Sponsor organisation

University Of Ottawa Heart Institute

Address

40 Ruskin Street

City

Ottawa

Postcode

K1Y 4W7

Country

Canada

Scientific contact point

Organisation

University Of Ottawa Heart Institute

Contact name

Sonya Jancar

Public contact point

Organisation

University Of Ottawa Heart Institute

Contact name

Sonya Jancar

Locations

2 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 25 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications