Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia

Conditions

S. aureus (meticillin-susceptible or resistant) infection, acute infection Infections and Infestations Staphylococcus aureus as the cause of diseases classified to other chapters

Guy Thwaites, Matthew Scarborough, Alexander J. Szubert, Pedro Saramago, Marta Soares et al. (41 authors)

Health Technology Assessment2018-10-0115 citations

10.3310/hta22590

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

Thwaites GE, Scarborough M, Szubert A, Nsutebu E, Tilley R, Greig J, Wyllie SA, Wilson P, Auckland C, Cairns J, Ward D, Lal P, Guleri A, Jenkins N, Sutton J, Wiselka M, Armando GR, Graham C, Chadwick PR, Barlow G, Gordon NC, Young B, Meisner S, McWhinney P, Price DA, Harvey D, Nayar D, Jeyaratnam D, Planche T, Minton J, Hudson F, Hopkins S, Williams J, Török ME, Llewelyn MJ, Edgeworth JD, Walker AS, United Kingdom Clinical Infection Research Group (UKCIRG).

2017-12-14137 citations

10.1016/s0140-6736(17)32456-x

Interventions

2 weeks of rifampicin or placebo in addition to standard antibiotic therapy

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Adults (18 years or older) 2. Staphylococcus aureus (meticillin-susceptible or resistant) grown from at least one blood culture 3. Less than 96 hours of active antibiotic therapy for the current infection (added 09/11/2016: not including rifampicin and excluding stat doses) 4. Patient or legal representative (LR) provides written informed consent

Exclusion criteria

Exclusion criteria: 1. Infection not caused by S. aureus alone in the opinion of the treating physician (e.g. S. aureus is considered a blood culture contaminant, or polymicrobial culture with another organism likely to be contributing clinically to the current infection) 2. Sensitivity results already available and demonstrate rifampicin resistant S. aureus (defined by British Society for Antimicrobial Chemotherapy in vitro disc susceptibility testing) 3. Treating physician considers rifampicin is contraindicated for any reason 4. Treating physician considers rifampicin treatment is mandatory for any reason 5. Suspected active infection with Mycobacterium tuberculosis 6. Previously been randomised in ARREST for a prior episode of S. aureus bacteraemia

Design outcomes

Primary

Measure	Time frame
Current primary outcome measures as of 09/11/2016: Bacteriological failure/death through 12 weeks from randomisation Previous primary outcome measures: 1. All cause mortality through 14 days from randomisation 2. Bacteriological failure/death through 12 weeks from randomisation	—

Secondary

Measure	Time frame
Current secondary outcome measures as of 09/11/2016: 1. All cause mortality through 14 days from randomisation 2. Death or clinically defined treatment failure or disease recurrence by 12 weeks (clinical failure being assessed by an independent endpoint committee blind to the treatment allocation) 3. Duration of bacteraemia (blood cultures will be taken on days 3 and 7 following randomisation) 4. Adverse events (grade 3/4 adverse events, serious adverse events) 5. Modification of any treatment (including concomitant medications) due to drug interactions 6. Development of rifampicin resistant S. aureus 7. Cost-effectiveness of rifampicin Previous secondary outcome measures: 1. Death or clinically defined treatment failure or disease recurrence by 12 weeks (clinical failure being assessed by an independent endpoint committee blind to the treatment allocation) 2. Duration of bacteraemia (blood cultures will be taken on days 3 and 7 following randomisation) 3. Adverse events (grade 3/4 adverse events, serious adverse events) 4. Modification of any treatment (including concomitant medications) due to drug interactions 5. Development of rifampicin resistant S. aureus	—

Measure

Time frame

Current secondary outcome measures as of 09/11/2016: 1. All cause mortality through 14 days from randomisation 2. Death or clinically defined treatment failure or disease recurrence by 12 weeks (clinical failure being assessed by an independent endpoint committee blind to the treatment allocation) 3. Duration of bacteraemia (blood cultures will be taken on days 3 and 7 following randomisation) 4. Adverse events (grade 3/4 adverse events, serious adverse events) 5. Modification of any treatment (including concomitant medications) due to drug interactions 6. Development of rifampicin resistant S. aureus 7. Cost-effectiveness of rifampicin Previous secondary outcome measures: 1. Death or clinically defined treatment failure or disease recurrence by 12 weeks (clinical failure being assessed by an independent endpoint committee blind to the treatment allocation) 2. Duration of bacteraemia (blood cultures will be taken on days 3 and 7 following randomisation) 3. Adverse events (grade 3/4 adverse events, serious adverse events) 4. Modification of any treatment (including concomitant medications) due to drug interactions 5. Development of rifampicin resistant S. aureus

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Countries

United Kingdom

Outcome results

None listed