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| [ Print-friendly version ] |
| Adjunctive Rifampicin to Reduce Early mortality from STaphylococcus aureus bacteraemia |
| ISRCTN | ISRCTN37666216 |
| ClinicalTrials.gov identifier | |
| Public title | Adjunctive Rifampicin to Reduce Early mortality from STaphylococcus aureus bacteraemia |
| Scientific title | Adjunctive Rifampicin to Reduce Early mortality from STaphylococcus aureus bacteraemia: a multi-centre, randomised, double blind, placebo controlled trial |
| Acronym | ARREST |
| Serial number at source | ARREST |
| Study hypothesis | Adjunctive rifampicin will enhance killing of S. aureus early in the course of antibiotic treatment, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death |
| Lay summary |
Background and study aims
Staphylococcus (S) aureus is a bacteria normally found on the skin. It can cause severe infections, with a reputation as a ‘super-bug’ when it is resistant to antibiotics, for example, meticillin-resistant S. aureus ( MRSA). In the community S. aureus causes serious skin infections (e.g. cellulitis), whilst in hospital it may infect wounds, intravenous lines (used to inject drugs or fluids) and other implanted medical devices (e.g. artificial heart valves and joints). S. aureus is especially dangerous when it infects the bloodstream (bacteraemia). Despite the incidence of S. aureus bacteraemia the best way to treat this infection remains uncertain. Doctors do not know which antibiotics are the most effective, how long these should be given, and whether starting treatment with a combination of antibiotics is better than starting with just one. Current UK guidelines recommend at least 14 days treatment with a single antibiotic for S. aureus bacteraemia, but acknowledge the lack of evidence supporting this recommendation. We want to find out whether or not giving an extra antibiotic, called rifampicin, in addition to the standard antibiotic, will help sick people with S. aureus blood infections. We want to know if rifampicin prevents some of them from dying, or whether it makes no difference to survival but just gives more side-effects and/or encourages the bug to become resistant. At the moment we do not know whether taking extra rifampicin is better or the same or even worse – this is the reason we are doing the study. Who can participate? Patients admitted to hospital who are found to have S. aureus infection. What does the study involve? ARREST is designed as a placebo-controlled trial. A placebo is a dummy treatment such as a pill which looks like the real treatment (rifampicin) but it contains no active ingredient. Everyone in the study will get the same standard antibiotic that they would have received if they decided not to join the study. In addition , you will have an equal chance of getting rifampicin for 2 weeks or getting a placebo which looks like rifampicin for 2 weeks on top of this standard antibiotic. Whether you get extra rifampicin or extra placebo will be chosen by chance by a computer. What are the possible benefits and risks of participating? Benefits: Taking rifampicin may help you fight S. aureus blood infection better. Whether you get rifampicin or a placebo, we will monitor you very carefully throughout your treatment and detect early any complications of the infection or side-effects of the drugs. Entering this study may not directly benefit you, but the information we get from the ARREST study will help to guide the best way to treat patients like you in the future Risks: Rifampicin, like all medicines, has unwanted side-effects, which are sometimes serious. Serious side effects happen in fewer than 1 in 100 people and it may be necessary to stop the study drug after which the problem usually goes away. The most important side-effect of rifampicin is that is can cause inflammation of the liver. This can cause vomiting and abdominal pain. Regular blood tests will be performed during the study to watch for this side-effect. The other common side-effect of rifampicin is that it can turn urine, tears and sweat an orange colour. This is completely harmless and goes away completely when the drug is stopped. Finally, rifampicin increases the way the body breaks down some drugs. This can mean that these drugs become less effective. For example, rifampicin can stop the oral contraceptive pill working. The study doctor will check with the you what medication you are on before starting the study so that she/he can ensure rifampicin will not effect you. Where is the study run from? The study will take place across several clinics in National Health Service (NHS) hospitals across the UK. When is the study starting and how long it is expected to run for? The study will start in April 2012 and will run for four years. You will be followed up for 12 weeks, and more information on health status may be obtained by looking at medical notes for five years thereafter. Who is funding the study? The National Institute of Health Research. Who is the main contact? Dr Guy Thwaites guy.thwaites@gstt.nhs.uk |
| Ethics approval |
Not provided at time of registration
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| Study design |
Parallel group randomised double-blind placebo-controlled multi-centre trial
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| Countries of recruitment | United Kingdom |
| Disease/condition/study domain |
S. aureus (meticillin-susceptible or resistant) infection, acute infection
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| Participants - 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 4. Patient or legal representative (LR) provides written informed consent |
| Participants - 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 |
| Anticipated start date | 01/10/2012 |
| Anticipated end date | 07/01/2016 |
| Status of trial | Ongoing |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | 940 |
| Interventions |
2 weeks of rifampicin or placebo in addition to standard antibiotic therapy
|
| Primary outcome measure(s) |
1. Al cause mortality through 14 days from randomisation
2. Bacteriological failure/death through 12 weeks from randomisation |
| Secondary outcome measure(s) |
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 |
| Sources of funding | NIHR Health Technology Assessment Programme - HTA (UK) ref: 10/104/25 |
| Trial website | |
| Publications | |
| Contact name | Dr Guy Thwaites |
| Address |
Centre for Clinical Infection and Diagnostics Research
King's College London Guy’s and St. Thomas’ Hospital |
| City/town | London |
| Zip/Postcode | SE1 9RT |
| Country | United Kingdom |
| Sponsor | Medical Research Council (MRC) (UK) |
| Address |
Regional Centre London
Aviation House 125 Kingsway |
| City/town | London |
| Zip/Postcode | WC2B 6NH |
| Country | United Kingdom |
| Sponsor website: | http://www.mrc.ac.uk/ |
| Date applied | 20/01/2012 |
| Last edited | 26/01/2012 |
| Date ISRCTN assigned | 26/01/2012 |
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| © 2012 ISRCTN unless otherwise stated. | |
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