BRAIN AF

The main objective of this study is to evaluate safety and effectiveness of rivaroxaban (anticoagulant) compared to standard of care [placebo for subjects without vascular disease or Aspirin® for subjects with vascular disease] in reducing stroke and cognitive deficits in people with atrial fibrillation and a low risk of stroke. A reduced dose of rivaroxaban 15 mg per day will be used in this study.

If you are eligible to participate in this study, you will be randomly assigned (like a coin toss) to one of the two groups of treatment:

• Rivaroxaban
• Usual care: Aspirin for patients with vascular disease, placebo for all others

The BRAIN-AF study is a double-blind study, meaning that neither you nor the research team know which treatment you receive. However, in an emergency, if it is required, this information can be obtained by the study doctor.

The study drugs, as well as instructions on how to take them will be given to you by the research team. We will ask you to take the study medication once daily at the same time and with a meal, for the duration of your follow-up in the study.

The study will consist of visits every 6 months, either in clinic or by telephone/video-conferencing, up to 14 visits in total. Video conferencing will be done with the University of Calgary ZOOM account and require a password for entry to ensure your privacy and security. ZOOM visits will be recorded only locally. These visits will take 15-60 minutes of your time.

These visits will include:

• Medical history and brief physical exam
• Blood samples at some visits and a urine or blood sample for pregnancy if appropriate
• ECG
• Questionnaires about your quality of life and thinking
• Questions regarding side effects of study medications and changes in other medications
• Questions about the atrial fibrillation
• Return of study drug bottles and resupply

As a subject participating in a research project, you will have certain responsibilities which are as follows:

• Avoid participating simultaneously in several research projects;
• Keep the study drugs out of reach of children;
• Tell your study doctor about all medicines you are taking, including prescription and nonprescription drugs and natural products;
• Tell your study doctor about all medical problems, doctor visits, hospital visits and medical procedures that you had have during your participation in the study;
• Inform as soon as possible your study doctor if you need to cancel an appointment. A new appointment will be scheduled;
• At the beginning of the study, we will give you an information card with details of the study and how to contact your doctor in case of emergency. You should always carry this card with you during the study;
• Do not take the following drugs
  • Azoles antifungal (ex. ketoconazole)
  • Inhibitors of HIV protease (ex. ritaronavir)

Rivaroxaban and Aspirin® (acetylsalicylic acid) are drugs already commonly used and are approved by Health Canada and the Food and Drug Administration (FDA) of the United States for use in reducing the risk of stroke in patients with AF. As a result, adverse effects of these drugs are already documented.

• It is not known whether rivaroxaban and Aspirin® causes side effects to pregnant women, to an unborn child, or to children of breastfeeding women. Because of these unknown risks, if you are pregnant or trying to become pregnant you cannot participate in the study. Similarly, if you are breastfeeding a child, you cannot participate in the study.

Blood samples for laboratory analysis may cause a mild swelling, bruising/bleeding at the puncture site and/or fainting associated with the blood draw procedure. Blood sampling rarely causes infection.

ECGs are routine procedures in clinical practice, however some minor skin irritation is possible at the site of the electrode adhesive.

COVID 19 Related Risks: As some of visits for this study must be done in person to allow for tests and procedures, there is an added risk of you being exposed to COVID 19 from other people within the facility or by use of public transit to attend your appointment. We have several measures in place to reduce this risk as much as possible including screening each patient who attends our facility, use of PPE for all staff and patients, restrictions on the number of people allowed within the space, enhanced general cleaning procedures and sanitization of any space a patient occupies immediately following their visit.

Although participation in this study may be of no benefit to you personally, it is hoped that what is learned here will be of future benefit to others suffering from AF.