Dabigatran vs. Oral Anti-Xa Inhibitors in S. Aureus Bacteremia

Dabigatran vs. Oral Anti-Xa Inhibitors in S. Aureus Bacteremia

This is an open-label randomized controlled trial which will enroll patients with S. aureus bacteremia who are already taking oral anticoagulant medications (apixaban, edoxaban, or rivaroxaban) for an approved indication (stroke prevention in atrial fibrillation, prevention or treatment of venous thromboembolism). We will randomize patients to continue their existing medication or change to another medication (dabigatran) which is approved for the original indication.

Dabigatran is approved in many countries for the treatment or prevention of venous thromboembolism or preventing stroke in atrial fibrillation. Unlike the other medications listed above, dabigatran seems to have activity against S. aureus in the test tube, in animal models, and in a smaller randomized controlled trial. We wish to determine if changing to dabigatran will improve outcomes in S. aureus bacteremia in people who otherwise would have a reason to be taking it.

This study is an approved sub-study of The Staphylococcus aureus Network Adaptive Platform (SNAP) trial (NCT05137119).

If positive, this study will support a second RCT in people who do not currently have an indication for anticoagulation.

The participant must meet all inclusion and exclusion criteria for the SNAP Platform (NCT05137119) and also the following inclusion and exclusion criteria:

Inclusion Criteria:

• Patient is taking (or will imminently start taking) an oral Xa inhibitor (e.g., apixaban, edoxaban, rivaroxaban) for: stroke prevention in atrial fibrillation, treatment or secondary prevention of deep venous thrombosis or pulmonary embolism, prevention of VTE in patients who have undergone elective total hip or total knee replacement surgery provided there are 30 or more days of planned treatment remaining at the time of enrolment.

Exclusion Criteria:

• Active bleeding as determine by the site investigator after discussion with the treating team (patient may remain eligible for up to 120 hours from platform entry if condition is resolved and antithrombotic therapy is resumed)
• Anticipated major cardiac surgery, neurosurgery, or spine surgery within the next 3 days
• Known pregnancy (with testing available for women with childbearing potential)
• Known use of dabigatran within last month
• Allergy to dabigatran
• Concomitant use of amiodarone, ketoconazole, rifampin, verapamil, clopidogrel, prasugrel, or ticagrelor
• eGFR < 30mL/minute calculated by Cockcroft-Gault equation using adjusted weight [patient may remain eligible for up to 120 hours from platform entry if acute kidney injury is resolved such that antithrombotic therapy can be safely resumed/prescribed]
• Off label use (e.g., metallic mechanical heart valve, left ventricular thrombus, antiphospholipid antibody syndrome)