The CLOPI-SNAP study is a randomized, multicenter, open-label clinical trial embedded within the SNAP (NCT 05137119) research platform. It constitutes a sub-study added to the core protocol for patients suffering Staphylococcus aureus bacteremia (SAB).

The CLOPI-SNAP study evaluates whether the administration of clopidogrel as adjunctive therapy improves clinical outcomes while maintaining an acceptable safety profile in hospitalized patients with Staphylococcus aureus bacteremia (SAB).

To be eligible for the SNAP platform (NCT 05137119), patients must meet at least two criteria: isolation of the Staphylococcus aureus complex from ≥1 blood culture and admission to a participating hospital at the time of eligibility assessment. SNAP is designed to concurrently evaluate multiple therapeutic strategies. Patients are randomly assigned to different concurrent treatment options that are currently considered acceptable in routine clinical practice; thus, standard-of-care therapy consists of approved antibiotics for the treatment of Staphylococcus aureus infection.

Specifically, patients participating in CLOPI-SNAP-adult patients with SAB enrolled in the SNAP platform-are randomized in a 1:1 ratio to receive either oral clopidogrel for 5 days, administered as a 300-mg loading dose on Day 1 followed by 75 mg once daily on subsequent days, or no antiplatelet therapy. The primary endpoint is the Desirability of Outcome Ranking (DOOR) assessed at Day 90, a hierarchical composite outcome integrating survival, clinical failure, infectious complications, and the occurrence of serious adverse events. The limited 5-day duration of clopidogrel administration is intended to focus its potential therapeutic benefit on the early phase of infection, characterized by high bacterial burden and systemic inflammation, while minimizing the risk of bleeding associated with prolonged antiplatelet exposure.

Inclusion Criteria:

To be eligible, patients must meet the same criteria as those of the general SNAP platform, as well as the domain-specific criteria:

• Microbiological isolation: Presence of Staphylococcus aureus complex in at least one blood culture.
• Hospitalization status: The patient must be admitted to a participating hospital at the time of eligibility assessment.
• Time window: Eligibility assessment must be completed within 72 hours after collection of the initial blood culture.

Exclusion Criteria:

General Medical and Safety Factors:

• Allergies: Known hypersensitivity to thienopyridines (clopidogrel, prasugrel, ticlopidine).
• Clinical status: Inability to tolerate or take oral medications, and severe hepatic impairment (Child-Pugh Class C).
• Pregnancy: Pregnant or breastfeeding women.

High Risk of Bleeding or Hematologic Disorders:

• Active or recent bleeding: Significant bleeding or invasive procedures within the previous 7 days.
• Planned surgeries: Requirement for major surgical intervention within 10 days following study enrollment.
• Coagulation parameters: Platelet count <50,000/mm³ or known coagulation disorders.
• Concomitant medications: Patients already receiving regular aspirin therapy, other P2Y12 inhibitors, or therapeutic-dose anticoagulants (prophylactic-dose heparin is permitted).

Specific Diagnoses and Clinical Criteria:

• Endocarditis: Confirmed diagnosis or clinical suspicion of bacterial endocarditis. Sources indicate that exclusion of endocarditis is justified because the potential benefit of clopidogrel is expected during early phases of high bacterial burden, whereas bleeding risk increases with prolonged treatment or established deep-seated infections.
• Medical judgment: If the treating clinical team determines that participation in this domain is not in the patient's best interest.

The information will be made available upon completion of the study. During the study period and data preparation phase, the information will be under the custody and responsibility of the research team.