Clopidogrel vs. Aspirin for Staph Bloodstream Infection

(Clopido-SNAP Trial)

Overseen By Lina Petrella

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Todd C. Lee MD MPH FIDSA

Must be taking: Aspirin

Must not be taking: Clopidogrel, Prasugrel, Ticagrelor, Xa inhibitors

Disqualifiers: Active bleeding, Major surgery, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

300 Participants Needed

Trial Summary

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 aspirin for secondary prevention of cardiovascular events. We will randomize patients to continue their aspirin or change clopidogrel which is also approved for secondary prevention. Unlike aspirin, clopidogrel may have activity against S. aureus. We wish to determine if changing to clopidogrel 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 clopidogrel.

Will I have to stop taking my current medications?

If you are taking aspirin for heart-related issues, you may be asked to switch to clopidogrel for the trial. The protocol does not specify if you need to stop other medications, so it's best to discuss with the trial team.

What data supports the effectiveness of the drugs Clopidogrel and Aspirin for Staph bloodstream infection?

While there is no direct evidence for Staph bloodstream infections, Clopidogrel and Aspirin together have been shown to reduce the risk of serious heart-related events in patients with certain heart conditions, compared to Aspirin alone. This suggests that the combination might offer enhanced benefits in other conditions as well. ^{1 2 3 4 5}

Is it safe to use clopidogrel and aspirin together?

Studies have shown that using clopidogrel and aspirin together is generally safe for humans, but it can increase the risk of bleeding, especially in patients who need additional blood-thinning medications. This combination is often used for heart-related conditions and stroke prevention, and while it can be effective, it's important to monitor for any bleeding complications. ^{2 4 6 7 8}

How does the drug combination of Clopidogrel and Aspirin differ from other treatments for Staph bloodstream infection?

The combination of Clopidogrel and Aspirin is unique because it involves dual antiplatelet therapy, which is typically used to prevent blood clots in heart disease, but is being explored for its potential benefits in treating Staph bloodstream infections. This approach is novel as it targets the blood's clotting process, which is not a standard treatment for infections. ^{1 2 3 9 10}

Research Team

Todd C Lee, MD MPH

Principal Investigator

Research Institute of the McGill University Health Centre

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 using aspirin to prevent heart problems. It's part of a larger study and may lead to another trial if results are positive.

Inclusion Criteria

I am taking aspirin to prevent further heart or blood vessel disease.

Exclusion Criteria

Allergy to clopidogrel

I am currently taking an oral Xa inhibitor medication.

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either continue aspirin or switch to clopidogrel for secondary prevention of cardiovascular events

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of clinical failure, adverse events, and mortality

12 weeks

Treatment Details

Interventions

• Aspirin
• Clopidogrel

Trial Overview The study compares the effects of continuing aspirin versus switching to clopidogrel, which might help fight the bacterial infection, in improving patient outcomes.

Participant Groups

Group I: Change to clopidogrel Experimental Treatment 1 Intervention

Patients will have their aspirin discontinued and start clopidogrel.

Group II: Continue aspirin Active Control 1 Intervention

Patients will continue their existing aspirin

Aspirin is already approved in European Union, United States, Canada, China for the following indications:

Approved in European Union as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in United States as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in Canada as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in China as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention

Who Is Running the Clinical Trial?

Todd C. Lee MD MPH FIDSA

Lead Sponsor

Trials

3

Recruited

660+

Findings from Research

In a study of 70 patients who had recently experienced an ischemic stroke, combining clopidogrel with aspirin (C+ASA) resulted in significantly greater inhibition of platelet activity compared to aspirin alone (ASA), indicating enhanced antiplatelet protection.

The C+ASA treatment led to notable reductions in various platelet activation markers and microparticle formation, with no serious adverse events reported, suggesting it is a safe and effective option for improving platelet inhibition in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of clopidogrel and aspirin in combination versus aspirin alone on platelet activation and major receptor expression in patients after recent ischemic stroke: for the Plavix Use for Treatment of Stroke (PLUTO-Stroke) trial. Serebruany, VL., Malinin, AI., Ziai, W., et al.[2018]

References

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

Clopidogrel added to aspirin versus aspirin alone in secondary prevention and high-risk primary prevention: rationale and design of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial. [2018]

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

Interpreting the CHARISMA study. What is the role of dual antiplatelet therapy with clopidogrel and aspirin? [2019]

3. England pubmed.ncbi.nlm.nih.gov

Prevention of coronary heart disease with aspirin and clopidogrel: efficacy, safety, costs and cost-effectiveness. [2022]

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

Effects of clopidogrel and aspirin in combination versus aspirin alone on platelet activation and major receptor expression in patients after recent ischemic stroke: for the Plavix Use for Treatment of Stroke (PLUTO-Stroke) trial. [2018]

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

Comparative effect of clopidogrel and aspirin versus aspirin alone on laboratory parameters: a retrospective, observational, cohort study. [2021]

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

Dual antiplatelet therapy in stroke and ICAS: Subgroup analysis of CHANCE. [2021]

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

Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement in patients with an indication for anticoagulation. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Future perspectives for optimizing oral antiplatelet therapy. [2017]

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

Antiplatelet Therapy in Staphylococcus aureus Bacteremia: No Time Like the Past? [2022]

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

Ticagrelor and the risk of Staphylococcus aureus bacteraemia and other infections. [2022]