The use of P2Y12 receptor inhibitors such as clopidogrel and ticagrelor, which possess both antistaphylococcal and platelet-modulating properties, are currently under investigation as potential strategies against SAB. Ticagrelor in particular, has shown to have in vitro and in vivo killing activity against S. aureus, with the proposed mechanisms of action including enhancing platelet-mediated killing of S. aureus by inhibiting the actions of S. aureus alpha-toxin and preventing the adhesion of S. aureus to host tissues.

Although a general protective role of P2Y12 inhibitors was observed across studies, it is important to highlight that all were non-randomised and subject to uncontrolled confounding, limiting any causal interpretations - even when assessing secondary outcomes. Both ticagrelor and clopidogrel also carry potential life-threatening risks, including bleeding. This demonstrates a need to not only test these agents in a randomised controlled trial, but to also consider whether sufficient clinical equipoise exists to justify exposing patients to such risks. In this regard, initially testing clopidogrel, which is associated with lower bleeding risk, may be a more appropriate starting point.

Patients are eligible for this domain if they meet all of the platform-level inclusion and non of the platform-level exclusion criteria AND all of the domain-level inclusion and none of the domain-level exclusion criteria.

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Domain-specific inclusion criteria:

• The site is currently participating in the SNAP-Clopidogrel 1 domain.

Domain-specific exclusion criteria:

• Known allergy to thienopyridine, specifically clopidogrel, prasugrel, and ticlopidine
• Patient is <18 years of age
• Not able to tolerate or assume oral drugs
• Class C Child-Pugh liver disease
• Active haemorrhage, recent major bleeding episode, or invasive procedure at the time of domain eligibility assessment or within the previous 7 days
• Invasive procedure likely to be performed within the 10 days following platform entry
• Suspected or proven bacterial endocarditis diagnosis
• Platelet count <50,000/mm3 from a blood sample obtained on the day of domain eligibility assessment or on the two prior calendar days
• Known coagulation disorder
• Currently receiving:
  
  • Regular aspirin
  • Regular P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor)
  • Therapeutic dose anticoagulants
• Pregnant/breastfeeding women
• Treating clinician deems participation in this domain is not in the subject's best interest
• At the time of domain eligibility assessment, more than 72 hours has elapsed since index blood culture collection

Participants will be randomised to one of the following:

• Oral clopidogrel arm
  
  • Oral clopidogrel 75mg pills
    
    • 300mg from domain reveal (1x)
    • 75mg daily until 5 calendar days of treatment has been achieved (4x)
• No antiplatelet treatment arm

Lead Investigator: Dr. Jesús Rodríguez Baño

Email: jesusrb@us.es