Every year in England, around 13,000 people develop a Staphylococcus aureus bloodstream infection, and 15 to 30 percent die within 90 days. Despite this, fewer than 3,000 patients have ever been recruited into randomised trials to determine which antibiotic works best. The SNAP trial aims to fix that gap by testing multiple antibiotic strategies in a single, adaptive platform study that can adjust treatments mid-trial based on emerging results. It compares different antibiotic backbones, tests whether adding clindamycin helps, and evaluates whether switching patients to oral antibiotics earlier is safe. If successful, the trial could produce the first robust evidence to guide treatment guidelines from NICE and international bodies, replacing guesswork with data. The NHS currently spends over £150 million per year on hospital stays alone for these patients, so even a modest improvement in outcomes or a reduction in length of stay could save money while saving lives. This is a pragmatic, large-scale trial designed to change practice worldwide.
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The Staphylococcus aureus network adaptive platform (SNAP) trial investigates a range of antibiotic treatment options in S. aureus bacteraemia (SAB). Background: S. Aureus bloodstream infection (bacteraemia) is a common, severe global infection. SAB affects ~13000 people/year in England with 15-30% 90-day mortality. Treatment is based on antibiotic susceptibility but we lack evidence to support antibiotic selection with <3000 participants ever recruited into randomised controlled trials (RCT). There are no specific SAB international or UK guidelines. Pragmatic clinical trials are urgently needed, to optimise antibiotic choice and improve outcomes. Aims & Objectives: SNAP will investigate a range of antibiotic treatment options in SAB. The overall aim is to optimise treatment for SAB. The initial platform comprises 3 domains as below: A. Antibiotic backbone: - Flucloxacillin (control) vs. cefazolin (intervention) in methicillin-susceptible SAB - Flucloxacillin (control) vs. penicillin (intervention) in penicillin-susceptible SAB - Standard of care antibiotic (control, usually vancomycin) vs. SOC antibiotic + cefazolin (intervention) in methicillin-resistant S. aureus (MRSA) bacteraemia B. Adjunctive clindamycin: - No additional treatment (control) vs. adjunctive clindamycin (intervention) in all SAB C. Early oral switch: - Antibiotic intravenous backbone treatment as per current care (control) vs. early oral switch algorithm (intervention) in all SAB Methods: SNAP is an international, adaptive platform, open label RCT of hospital inpatients with SAB (www.snaptrial.com.au). >20% of 6000 patients will be recruited from the UK across NHS networks. Participants will be factorially allocated across each of the three study domains. Key inclusion: patients with SAB admitted hospital; key exclusions: polymicrobial bacteraemia, treatment with non-trial systemic antibiotics, SAB diagnosed >72 hr ago. The primary outcome is all-cause mortality at 90 days. Secondary outcomes include all-cause mortality at 14, 28 and 42 days, duration of survival, hospital length of stay, microbiological treatment failure, development of new metastatic foci, C. difficile diarrhoea and health economic costs. Selected domains will use response-adaptive randomisation and the design utilises adaptive trial methodology including frequent interim analyses using Bayesian hierarchical approaches. Impact and Dissemination: Based on existing costing data, the total cost per year to the NHS for the hospital stay alone for SAB patients would be expected to exceed £150million/year in England alone. We anticipate the study itself will be cost-saving irrespective of the outcomes. As the largest RCT of SAB treatment ever conducted it will be of global significance resulting in worldwide changes to practice. Dissemination will be via international networks, conferences, publications, and the SNAP Patient and public involvement group communications. The evidence base provided by SNAP will be used in NICE and other international SAB treatment guidelines, ultimately resulting in improved outcomes from an infection with unacceptably high morbidity and mortality, and cost.
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