Adjuvant Clopidogrel in Staphylococcus Aureus Bacteremia

Official title

Phase 2 Platform Randomized, Multicentre and Open Trial on the Efficacy and Safety of Clopidogrel as Adjuvant Drug in Staphylococcus Aureus Bacteraemia (CLOPI-SNAP)

Overview

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).

Detailed description

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.

Interventions

• Drug Clopidogrel
  Oral clopidogrel 75 mg pills; 300 mg from domain reveal (day 1 of treatment), followed by 75 mg daily until day 5 of treatment inclusive (4 additional calendar days)
• Drug No antiplatelet treatment
  Different concurrent antibiotic options currently approved for SAB

Primary outcome measures

• Desirability of Outcome Ranking (DOOR) [Time frame: At day 90 from day 0.]

Secondary outcome measures (4)

• Mortality [Time frame: At day 14 and day 28 from day of assignment of study drug (day 0)]
• Length of stay of inpatient hospitalisation [Time frame: At day 90 from day 0.]
• Microbiological treatment failure [Time frame: At day 14 and day 90 from day of assignment of study drug (day 0)]
• New foci of infection [Time frame: At day 14 and day 90 from day of assignment of study drug (day 0)]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 20 centers

• Hospital General Universitario de Alicante — Alicante
• H.U. Clinic — Barcelona
• H.U. Mutua Terrassa — Barcelona
• Hospital del Mar — Barcelona
• Hospital Universitario Bellvitge — Barcelona
• Hospital Universitario de la Santa Creu i Sant Pau — Barcelona
• Hospital Universitario Vall d'Hebron — Barcelona
• H.U. Reina Sofía — Córdoba
• … and 12 more centers

Publications

• Campbell AJ, Anpalagan K, Best EJ, Britton PN, Gwee A, Hatcher J, Manley BJ, Marsh J, Webb RH, Davis JS, Mahar RK, McGlothlin A, McMullan B, Meyer M, Mora J, Murthy S, Nourse C, Papenburg J, Schwartz KL, Scheuerman O, Snelling T, Strunk T, Stark M, Voss L, Tong SYC, Bowen AC; Staphylococcus aureus Network Adaptive Platform Paediatric and Youth (SNAP-PY) working groupSNAP Global Trial Steering Comm PMID 39158898
• Mahar RK, McGlothlin A, Dymock M, Barina L, Bonten M, Bowen A, Cheng MP, Daneman N, Goodman AL, Lee TC, Lewis RJ, Lumley T, McLean ARD, McQuilten Z, Mora J, Paterson DL, Price DJ, Roberts J, Snelling T, Tverring J, Webb SA, Yahav D, Davis JS, Tong SYC, Marsh JA; SNAP Global Trial Steering Committee. Statistical documentation for multi-disease, multi-domain platform trials: our experience with the PMID 39934879
• Boyles T, Bowen AC, Chomba R, Nel J, Davis JS, Tong SYC. Inclusion of a low- and middle-income country site in the Staphylococcus aureus Network Adaptive Platform trial: experiences from Johannesburg. Clin Microbiol Infect. 2025 Dec;31(12):1948-1950. doi: 10.1016/j.cmi.2025.06.032. Epub 2025 Jul 4. No abstract available. PMID 40618922
• Walls G, McGrath L, Herdman MT, Campbell AJ, Cheng MP, Marks M, Ten Oever J, Sahng E, Yahav D, Tong SYC, Goodman AL, Lim AG, Bloomfield M; Staphylococcus aureus Network Adaptive Platform Early Oral Switch Domain Specific Working Group. Patient-reported Perceptions, Experiences, and Preferences Around Intravenous and Oral Antibiotics for the Treatment of Staphylococcus aureus Bacteremia: A Descript PMID 40988120
• de Kretser D, Mora J, Bloomfield M, Campbell A, Cheng MP, Guy S, Hensgens M, Kalimuddin S, Lee TC, Legg A, Mahar RK, Marks M, Marsh J, McGlothin A, Morpeth SC, Sud A, Ten Oever J, Yahav D, Bonten M, Bowen AC, Daneman N, van Hal SJ, Heriot GS, Lewis RJ, Lye DC, McQuilten Z, Paterson DL, Owen Robinson J, Roberts JA, Scarborough M, Webb SA, Whiteway L, Tong SYC, Davis JS, Walls G, Goodman AL; SNAP Ea PMID 37921609

Identifiers

NCT: NCT07384702 · CLOPI-SNAP · 2023-503582-35-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗