Staphylococcus aureus Network Adaptive Platform trial (SNAP)

Research summary

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.

Principal Investigator

Dr Matthew Scarborough

Contact us

Email: crndirectdeliveryteam@ouh.nhs.uk

IRAS number

1005342