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Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): study protocol for a randomised controlled trial.

Thwaites, G; Auckland, C; Barlow, G; Cunningham, R; Davies, G; Edgeworth, J; Greig, J; Hopkins, S; Jeyaratnam, D; Jenkins, N; et al. Thwaites, G; Auckland, C; Barlow, G; Cunningham, R; Davies, G; Edgeworth, J; Greig, J; Hopkins, S; Jeyaratnam, D; Jenkins, N; Llewelyn, M; Meisner, S; Nsutebu, E; Planche, T; Read, RC; Scarborough, M; Soares, M; Tilley, R; Török, ME; Williams, J; Wilson, P; Wyllie, S; Walker, AS; United Kingdom Clinical Infection Research Group (2012) Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): study protocol for a randomised controlled trial. Trials, 13 (241). 1 -14. ISSN 1745-6215 https://doi.org/10.1186/1745-6215-13-241
SGUL Authors: Planche, Timothy David

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Abstract

Background: Staphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection’s severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation. Methods: We will perform a parallel group, randomised (1:1), blinded, placebo-controlled trial in NHS hospitals across the UK. Adults (≥18 years) with S. aureus (meticillin-susceptible or resistant) grown from at least one blood culture who have received ≤96 h of active antibiotic therapy for the current infection and do not have contraindications to the use of rifampicin will be eligible for inclusion. Participants will be randomised to adjunctive rifampicin (600-900mg/day; orally or intravenously) or placebo for the first 14 days of therapy in combination with standard single-agent antibiotic therapy. The co-primary outcome measures will be all-cause mortality up to 14 days from randomisation and bacteriological failure/death (all-cause) up to 12 weeks from randomisation. 940 patients will be recruited, providing >80% power to detect 45% and 30% reductions in the two co-primary endpoints of death by 14 days and bacteriological failure/death by 12 weeks respectively. Discussion: This pragmatic trial addresses the long-standing hypothesis that adjunctive rifampicin improves outcome from S. aureus bacteraemia through enhanced early bacterial killing. If proven correct, it will provide a paradigm through which further improvements in outcome from S. aureus bacteraemia can be explored.

Item Type: Article
Additional Information: PubMed ID: 23249501. © 2012 Thwaites et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Anti-Bacterial Agents, Bacteremia, Clinical Protocols, Humans, Rifampin, Sample Size, Staphylococcal Infections, Science & Technology, Life Sciences & Biomedicine, Medicine, Research & Experimental, Research & Experimental Medicine, Staphylococcus aureus, Bacteraemia, Rifampicin, Mortality, CLINICAL-PRACTICE GUIDELINES, INFECTIOUS-DISEASES SOCIETY, METHICILLIN-RESISTANT, ANTIBIOTIC-TREATMENT, COMBINATION THERAPY, VANCOMYCIN, ENDOCARDITIS, OXACILLIN, MANAGEMENT, EMERGENCE, Staphylococcus aureus, Bacteraemia, Rifampicin, Mortality
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Trials
ISSN: 1745-6215
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Dates:
DateEvent
18 December 2012Published
Web of Science ID: WOS:000314237300001
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URI: https://openaccess.sgul.ac.uk/id/eprint/102067
Publisher's version: https://doi.org/10.1186/1745-6215-13-241

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