Condition category
Infections and Infestations
Date applied
20/01/2012
Date assigned
26/01/2012
Last edited
09/11/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
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
guy.thwaites@btinternet.com

Trial website

http://www.ctu.mrc.ac.uk/arrest/

Contact information

Type

Scientific

Primary contact

Prof Guy Thwaites

ORCID ID

Contact details

Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LJ
United Kingdom

Additional identifiers

EudraCT number

2012-00344-10

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

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

Trial setting

Hospitals

Trial 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

Phase

Not Applicable

Drug names

Rifampicin

Primary outcome measures

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

01/08/2012

Overall trial end date

17/01/2017

Reason abandoned

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

Patient

Age group

Adult

Gender

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

United Kingdom

Trial participating centre

Guy's and St Thomas' NHS Foundation Trust
SE1 9RT

Trial participating centre

Oxford University Hospitals NHS Trust
OX3 7LE

Trial participating centre

University College London Hospitals NHS Foundation Trust
NW1 2BU

Trial participating centre

Royal Free London NHS Foundation Trust
NW3 5NU

Trial participating centre

King's College Hospital NHS Foundation Trust
SE5 9RS

Trial participating centre

Brighton and Sussex University Hospitals NHS Trust
BN2 5BE

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
CB2 0QQ

Trial participating centre

Royal United Hospital Bath NHS Trust
BA1 3NG

Trial participating centre

Royal Devon and Exeter NHS Foundation Trust
EX2 5DW

Trial participating centre

Plymouth Hospitals NHS Trust
PL6 8DH

Trial participating centre

Hull and East Yorkshire Hospitals NHS Trust
HU3 2JZ

Trial participating centre

South Tees Hospitals NHS Foundation Trust
DL6 1JG

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
PO6 3LY

Trial participating centre

University Hospital Southampton NHS Foundation Trust
SO16 6YD

Trial participating centre

Blackpool Teaching Hospitals NHS Foundation Trust
FY3 8NR

Trial participating centre

The Leeds Teaching Hospital NHS Trust
LS1 3EX

Trial participating centre

University Hospitals Coventry and Warwickshire NHS Trust
CV2 2DX

Trial participating centre

Aintree University Hospital NHS Foundation Trust
L9 7AL

Trial participating centre

Bradford Teaching Hospitals NHS Foundation Trust
BD9 6RJ

Trial participating centre

County Durham and Darlington NHS Foundation Trust
DH1 5TW

Trial participating centre

Dartford & Gravesham NHS Trust
DA2 8DA

Trial participating centre

North Bristol NHS Trust
BS10 5NB

Trial participating centre

North Cumbria University Hospitals
CA2 7HY

Trial participating centre

University Hospitals of Leicester NHS Trust
LE1 5WW

Trial participating centre

Wirral University Teaching Hospital NHS Foundation Trust
CH49 5PE

Trial participating centre

The Newcastle upon Tyne Hospitals NHS Foundation Trust
NE7 7DN

Trial participating centre

Salford Royal NHS Foundation Trust
M6 8HD

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

http://www.mrc.ac.uk/

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

Federal/National Government

Location

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

Results - basic reporting

Publication summary

2012 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/23249501

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.