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?
National Institute of Health Research.
Who is the main contact?
Professor Guy Thwaites
guy.thwaites@btinternet.com
Study website
Additional identifiers
EudraCT/CTIS number
2012-00344-10
IRAS number
ClinicalTrials.gov 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
Acronym
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.
More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/1010425
Protocol can found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0003/81723/PRO-10-104-25.pdf
Ethics approval(s)
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
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
S. aureus (meticillin-susceptible or resistant) infection, acute infection
Intervention
2 weeks of rifampicin or placebo in addition to standard antibiotic therapy
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Not Applicable
Drug/device/biological/vaccine name(s)
Rifampicin
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 study start date
01/08/2012
Overall study end date
17/01/2017
Reason abandoned (if study stopped)
Eligibility
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(s)
Patient
Age group
Adult
Lower age limit
18 Years
Sex
Both
Target number of participants
770
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
26/11/2012
Recruitment end date
28/10/2016
Locations
Countries of recruitment
England, United Kingdom
Study participating centre
Guy's and St Thomas' NHS Foundation Trust
SE1 9RT
United Kingdom
Study participating centre
Oxford University Hospitals NHS Trust
OX3 7LE
United Kingdom
Study participating centre
University College London Hospitals NHS Foundation Trust
NW1 2BU
United Kingdom
Study participating centre
Royal Free London NHS Foundation Trust
NW3 5NU
United Kingdom
Study participating centre
King's College Hospital NHS Foundation Trust
SE5 9RS
United Kingdom
Study participating centre
Brighton and Sussex University Hospitals NHS Trust
BN2 5BE
United Kingdom
Study participating centre
The Royal Liverpool and Broadgreen University Hospitals NHS Trust
L7 8XP
United Kingdom
Study participating centre
Sheffield Teaching Hospitals NHS Foundation Trust
S10 2JF
United Kingdom
Study participating centre
Cambridge University Hospitals NHS Foundation Trust
CB2 0QQ
United Kingdom
Study participating centre
Royal United Hospital Bath NHS Trust
BA1 3NG
United Kingdom
Study participating centre
Royal Devon and Exeter NHS Foundation Trust
EX2 5DW
United Kingdom
Study participating centre
Plymouth Hospitals NHS Trust
PL6 8DH
United Kingdom
Study participating centre
Hull and East Yorkshire Hospitals NHS Trust
HU3 2JZ
United Kingdom
Study participating centre
South Tees Hospitals NHS Foundation Trust
DL6 1JG
United Kingdom
Study participating centre
Heart of England NHS Foundation Trust
B9 5SS
United Kingdom
Study participating centre
St George's Healthcare NHS Trust
SW17 0QT
United Kingdom
Study participating centre
Portsmouth Hospitals NHS Trust
PO6 3LY
United Kingdom
Study participating centre
University Hospital Southampton NHS Foundation Trust
SO16 6YD
United Kingdom
Study participating centre
Blackpool Teaching Hospitals NHS Foundation Trust
FY3 8NR
United Kingdom
Study participating centre
The Leeds Teaching Hospital NHS Trust
LS1 3EX
United Kingdom
Study participating centre
University Hospitals Coventry and Warwickshire NHS Trust
CV2 2DX
United Kingdom
Study participating centre
Aintree University Hospital NHS Foundation Trust
L9 7AL
United Kingdom
Study participating centre
Bradford Teaching Hospitals NHS Foundation Trust
BD9 6RJ
United Kingdom
Study participating centre
County Durham and Darlington NHS Foundation Trust
DH1 5TW
United Kingdom
Study participating centre
Dartford & Gravesham NHS Trust
DA2 8DA
United Kingdom
Study participating centre
North Bristol NHS Trust
BS10 5NB
United Kingdom
Study participating centre
North Cumbria University Hospitals
CA2 7HY
United Kingdom
Study participating centre
University Hospitals of Leicester NHS Trust
LE1 5WW
United Kingdom
Study participating centre
Wirral University Teaching Hospital NHS Foundation Trust
CH49 5PE
United Kingdom
Study participating centre
The Newcastle upon Tyne Hospitals NHS Foundation Trust
NE7 7DN
United Kingdom
Study participating centre
Salford Royal NHS Foundation Trust
M6 8HD
United Kingdom
Sponsor information
Organisation
Medical Research Council (MRC) (UK)
Sponsor details
MRC CTU at UCL
Aviation House
125 Kingsway
London
WC2B 6NH
United Kingdom
Sponsor type
Research council
Website
ROR
Funders
Funder type
Government
Funder name
Health Technology Assessment Programme
Alternative name(s)
NIHR Health Technology Assessment Programme, HTA
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Not provided at time of registration
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 18/12/2012 | Yes | No | |
| Results article | results | 01/10/2018 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |