Dabigatran for Staph Bloodstream Infection

(DABI-SNAP Trial)

Overseen By Lina Petrella

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Emily McDonald

Must be taking: Oral Xa inhibitors

Must not be taking: Dabigatran, Amiodarone, Ketoconazole, others

Disqualifiers: Active bleeding, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

300 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial may require you to switch from your current oral anticoagulant medication to dabigatran, but you won't have to stop taking anticoagulants altogether. The decision to switch will depend on the randomization process in the study.

Is dabigatran generally safe for humans?

Dabigatran, also known as Pradaxa, is generally used to prevent strokes in people with certain heart conditions, but it can cause serious bleeding, especially in people with kidney problems. There have been reports of severe bleeding, including a fatal case after a single dose, so it's important to use it under medical supervision. ^{1 2 3 4 5}

How does the drug Dabigatran differ from other treatments for Staph bloodstream infection?

Dabigatran is unique because it is primarily known as a blood thinner used to prevent blood clots, rather than an antibiotic, which is the standard treatment for Staph bloodstream infections. This suggests a novel approach to managing the condition, potentially targeting the body's response to infection rather than the bacteria directly. ^{6 7 8 9 10}

What is the purpose of this trial?

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 dabigratran 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.

Research Team

Emily G McDonald, MD MSC

Principal Investigator

Research Institute of the McGill University Health Centre

Eligibility Criteria

This trial is for patients with a Staphylococcus aureus blood infection who are already on oral anticoagulants like apixaban, edoxaban, or rivaroxaban. Participants must be taking these medications for conditions such as stroke prevention in atrial fibrillation or to prevent/treat blood clots.

Inclusion Criteria

I am currently on an oral Xa inhibitor for stroke prevention or treating blood clots.

Exclusion Criteria

Allergy to dabigatran

I have taken dabigatran in the last month.

I haven't had active bleeding in the last 5 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to continue their current anticoagulant or switch to dabigatran for the treatment of S. aureus bacteremia

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Dabigatran

Trial Overview The study tests if switching from current anticoagulant medication to dabigatran (which may fight S. aureus) improves patient outcomes. It's an open-label randomized trial where some continue their meds while others switch to dabigatran.

Participant Groups

Group I: Change to Dabigatran Experimental Treatment 1 Intervention

Patients will have their anticoagulation changed to dabigatran at the monograph approved dose for the indication, bleeding risk, and renal function.

Group II: Continue current anticoagulant Active Control 3 Interventions

Patients will continue their currently prescribed apixaban, edoxaban, or rivaroxaban

Who Is Running the Clinical Trial?

Emily McDonald

Lead Sponsor

Trials

2

Recruited

360+

University of Melbourne

Collaborator

Trials

193

Recruited

1,287,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Positive outcome after intentional overdose of dabigatran. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Bleeding with dabigatran (Pradaxa). [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Dabigatran etexilate (Pradaxa)--a new oral anticoagulant. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Dabigatran: will it change clinical practice? [2015]

5. England pubmed.ncbi.nlm.nih.gov

Fatal gastrointestinal hemorrhage after a single dose of dabigatran. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Early oral antibiotic switch in Staphylococcus aureus bacteraemia: The Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Early Oral Switch Protocol. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Case-Control Study of Telavancin as an Alternative Treatment for Gram-Positive Bloodstream Infections in Patients with Cancer. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Risk factors and management of Gram-positive bacteraemia. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Staphylococcus aureus bloodstream infections in older adults: clinical outcomes and risk factors for in-hospital mortality. [2022]

10. England pubmed.ncbi.nlm.nih.gov

A randomized Phase 2 trial of telavancin versus standard therapy in patients with uncomplicated Staphylococcus aureus bacteremia: the ASSURE study. [2022]