Condition category
Infections and Infestations
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English 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?
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. 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 November 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?
Professor Guy Thwaites

Trial website

Contact information



Primary contact

Prof Guy Thwaites


Contact details

Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)
Churchill Hospital
Old Road
United Kingdom

Additional identifiers

EudraCT number

2012-00344-10 number

Protocol/serial number

HTA 10/104/25

Study information

Scientific title

Adjunctive Rifampicin to Reduce Early mortality from STaphylococcus aureus bacteraemia: a multi-centre, randomised, double blind, placebo-controlled trial



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.

More details can be found at:
Protocol can found at:

Ethics approval

NRES Committee London - Westminster, 24/05/2012, ref:12/LO/0637

Study design

Parallel-group randomised double-blind placebo-controlled multi-centre trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet


S. aureus (meticillin-susceptible or resistant) infection, acute infection


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

Intervention type



Not Applicable

Drug names


Primary outcome measure

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 outcome measures

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

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant 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

Participant type


Age group




Target number of participants


Participant 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

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Guy's and St Thomas' NHS Foundation Trust

Trial participating centre

Oxford University Hospitals NHS Trust

Trial participating centre

University College London Hospitals NHS Foundation Trust

Trial participating centre

Royal Free London NHS Foundation Trust

Trial participating centre

King's College Hospital NHS Foundation Trust

Trial participating centre

Brighton and Sussex University Hospitals NHS Trust

Trial participating centre

The Royal Liverpool and Broadgreen University Hospitals NHS Trust
L7 8XP

Trial participating centre

Sheffield Teaching Hospitals NHS Foundation Trust
S10 2JF

Trial participating centre

Cambridge University Hospitals NHS Foundation Trust

Trial participating centre

Royal United Hospital Bath NHS Trust

Trial participating centre

Royal Devon and Exeter NHS Foundation Trust

Trial participating centre

Plymouth Hospitals NHS Trust

Trial participating centre

Hull and East Yorkshire Hospitals NHS Trust

Trial participating centre

South Tees Hospitals NHS Foundation Trust

Trial participating centre

Heart of England NHS Foundation Trust
B9 5SS

Trial participating centre

St George's Healthcare NHS Trust
SW17 0QT

Trial participating centre

Portsmouth Hospitals NHS Trust

Trial participating centre

University Hospital Southampton NHS Foundation Trust
SO16 6YD

Trial participating centre

Blackpool Teaching Hospitals NHS Foundation Trust

Trial participating centre

The Leeds Teaching Hospital NHS Trust

Trial participating centre

University Hospitals Coventry and Warwickshire NHS Trust

Trial participating centre

Aintree University Hospital NHS Foundation Trust
L9 7AL

Trial participating centre

Bradford Teaching Hospitals NHS Foundation Trust

Trial participating centre

County Durham and Darlington NHS Foundation Trust

Trial participating centre

Dartford & Gravesham NHS Trust

Trial participating centre

North Bristol NHS Trust
BS10 5NB

Trial participating centre

North Cumbria University Hospitals

Trial participating centre

University Hospitals of Leicester NHS Trust

Trial participating centre

Wirral University Teaching Hospital NHS Foundation Trust
CH49 5PE

Trial participating centre

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Trial participating centre

Salford Royal NHS Foundation Trust
M6 8HD

Sponsor information


Medical Research Council (MRC) (UK)

Sponsor details

Aviation House
125 Kingsway
United Kingdom

Sponsor type

Research council



Funder type


Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government


United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

2012 protocol in:

Publication citations

  1. Protocol

    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, , Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): study protocol for a randomised controlled trial., Trials, 2012, 13, 241, doi: 10.1186/1745-6215-13-241.

Additional files

Editorial Notes

09/11/2016: the following changes were made to the trial record: 1. The overall trial start date was changed from 01/10/2012 to 01/08/2012. 2. The overall trial end date was changed from 07/01/2016 to 17/01/2017. 3. The target number of participants was changed from 940 to 770.