Condition category
Infections and Infestations
Date applied
25/10/2012
Date assigned
26/10/2012
Last edited
24/02/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Clostridium difficile (bacteria) is a frequent cause of diarrhoea. It mostly affects older hospitalised patients, though more recently it has been seen in younger patients and indeed those who are not in hospital. This infection will often be successfully treated by antibiotics but has a high chance of returning (called a recurrence or relapse) which requires more treatment and/or prolonged hospital stay. It has been found that 1 in 4 patients may suffer a return of infection within 4 weeks of successful treatment. The purpose of this study is to look at whether treatment with a short course of an antibiotic called Rifaximin; taken straight after a standard course of antibiotic treatment, will be effective at reducing the likelihood of the infection returning.

Who can participate?
Men / Women aged 18 or over, who have been diagnosed with Clostridium difficile infection and are currently being / or have recently been treated with a course of Metronidazole and /or Vancomycin therapy. In order to take part your treatment must be successful. We will also include adults who lack mental capacity for whom we have a legal representative.

What does the study involve?
You will have already completed your normal treatment for Clostridium difficile successfully. Normal management would be to take no further treatment. If you agree to take part, you will be randomly assigned (equivalent to the toss of a coin) either to the active treatment or the placebo (the placebo will resemble the active treatment in every way except it will not contain any active ingredients). You will be asked to take two tablets three times a day for two weeks followed by one tablet three times a day for a further two weeks. We will ask you to a keep a daily record (diary) of your bowel frequency and consistency for this 4 week treatment period. We will ask you to provide us with a stool sample at the beginning and end of treatment, and a sample at 12 weeks after entering the study (or at any time during this period if the infection returns). You will be provided with a stool collection pack and a set of instructions on how to collect and store your stool sample. We will also request a 20ml blood sample (approximately 4 teaspoons) at week 4. The diary completion and stool and blood sampling are optional. We will phone you at two weeks to confirm that you are taking the right dose of medication and completing the diaries and again at 8 weeks to check progress. If possible, we would like you to visit us at 4 and 12 weeks to provide samples and return your stool diaries. If this is not possible, we will arrange to visit you in your home, whichever is more convenient. We would also like to find out whether your infection returns longer term. To do this we would like to contact you by telephone at 6 months.

What are the possible benefits and risks of participating?
One in four patients, completing a successful course of Metronidazole and Vancomycin may experience a return of their infection. We are anticipating that this will be lower in the group receiving Rifaximin but cannot guarantee this. Your taking part in this study will benefit future generations of patients and may reduce the chances of them suffering relapse. Rifaximin works differently from other antibiotics because it passes through your stomach and into your intestines without being absorbed into your blood stream, so it is very safe. Most people have no side effects though rarely nausea and headache have been reported and there is a very low risk of an allergic reaction developing. Giving a blood sample may cause discomfort or bruising though this usually resolves within a few days. Adults who lack mental capacity will not be required to provide a blood sample.

Where is the study run from?
The NIHR Nottingham Digestive Diseases Biomedical research unit at Nottingham University Hospitals is organising the research; trial coordination will take place at the Nottingham Clinical Trials Unit, University of Nottingham.

When is the study starting and how long is it expected to run for?
Recruitment will take place over a period of 2 years; enrolment is anticipated to start in November 2012.

Who is funding the study?
NIHR Research for Patient Benefit Programme, Department of Health, United Kingdom

Who is the main contact?
Nafisa Boota
nafisa.boota@nottingham.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Ms Sarah Fahy

ORCID ID

Contact details

Nottingham Clinical Trials Unit (NCTU)
Room 2000A
Nottingham Health Science Partners (NHSP)
C Floor
South Block
Queens Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom
-
rapid@nottingham.ac.uk

Additional identifiers

EudraCT number

2012-003205-10

ClinicalTrials.gov number

Protocol/serial number

12990

Study information

Scientific title

A randomised placebo controlled trial of "follow on" Rifaximin for the prevention of relapse of Clostridium associated diarrhoea

Acronym

RAPID

Study hypothesis

Clostridium difficile (C.diff.) infection is the main cause of antibiotic associated diarrhoea. It has historically mainly affects elderly hospitalised patients, although more recently a rising incidence of more virulent strains has been associated with infection in younger patients and those in the community. Clostridium difficile infection is characterised by a high incidence of recurrent infection which can have debilitating consequences on already weakened patients. There are few well designed clinical trials into this condition and treatment is largely based on experience and consensus opinion. Rifaximin is a poorly absorbed antibiotic which has been used for many years in Italy and the USA for the treatment of traveller's diarrhoea and IBS. It has an excellent safety record and has been shown to achieve high concentrations in the bowel. It has been used effectively to treat Clostridium difficile infection and has a low rate of antibiotic-resistance development. It has also been suggested as beneficial when used after an effective course of the antibiotic, metronidazole since it is said to disturb the normal gut bacteria less than metronidazole and vancomycin and hence might be predicted to reduce the incidence of relapse. We propose to test this hypothesis in our study. A reduction in recurrence rate of C Difficile from 30% to 5% would significantly reduce the burden of this disease in hospitals and the community and provide an inexpensive solution to this serious illness.

More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12990

Ethics approval

NRES Committee East Midlands - Leicester, First MREC approval date 31/08/2012, ref:12/EM/0292

Study design

Multicentre two-arm parallel-group double-blind randomised placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Condition

Clostridium difficile-associated diarrhea

Intervention

Patients randomised to receive either Rifaximin (200mg tablets) or placebo.

Dosage: Treatment is for 4 weeks. The initial trial daily dose will be 2 x 200mg tablets three times a day for first 2 weeks then, 1 x 200mg tablet three times a day for the final 2 weeks.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

The difference in % relapse between Rifaximin and placebo at week 12

Secondary outcome measures

Current secondary outcome measures as of 30/04/2015:
Clinical:
1. Proportion with relapse of CDAD within 6 months
2. Proportion rehospitalised for CDAD within 6 months
3. Length of in-hospital stay following start of treatment

Exploratory:
1. Stool frequency and consistency during 12 weeks after start of treatment
2. Microbiological assessments

Previous secondary outcome measures:
1. Bowel symptoms measured at weeks 1-4 and weeks 11-12
2. Length of stay on active versus placebo measured at week 12
3. Microbiological exploratory assessments measured at week 12
4. Safety/Adverse events measured at 6 months
5. The difference in relapse of CDAD within 6 months of start of therapy

Overall trial start date

11/12/2012

Overall trial end date

11/09/2016

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 30/04/2015:
1. Men / Women aged 18 and over (We will also include those adults who lack mental capacity for whom we have a legal representative)
2. Successful treatment of clinically diagnosed CDAD using standard therapy (metronidazole or vancomycin given according to standard local hospital guidelines)

Previous inclusion criteria:
1. Men / Women aged 18 and over (We will also include those adults who lack mental capacity for whom we have a legal representative)
2. Successful treatment of clinically diagnosed C. difficile-associated diarrhea (CDAD) using standard therapy (metronidazole or vancomycin given according to standard local hospital guidelines
3. Able to swallow tablets
4. Able to stop chronic antibiotic use
5. Women of child bearing potential willing and able to use at least one highly effective contraceptive method throughout the study. Acceptable contraceptive methods include: established use of oral, injected or implanted hormonal methods; placement of an intrauterine device (IUD) or intrauterine system (IUS); condom or occlusive cap (diaphragm or cervical/vault caps) with spermicide; true abstinence (when this is in line with the preferred and usual lifestyle of the participant); or vasectomised partner.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 180; UK Sample Size: 180

Participant exclusion criteria

Current exclusion criteria as of 24/02/2016:
1. Woman of childbearing potential and not willing to use at least one highly effective contraceptive method throughout the study*
2. Male with spouse/partner of childbearing potential and not willing to use condoms
3. Pregnant or breastfeeding
4. Unable to swallow tablets
5. Life expectancy of <4 weeks
6. Hypersensitivity to the active substance, to any rifamycin (e.g. rifampicin or rifabutin) or to any of its excipients (tablet core: sodium starch glycolate type A, glycerol distearate, colloidal anhydrous, silica, talc and microcrystalline cellulose. Tablet coating: hypromellose, titanium dioxide (E171), disodium edentate, propylene glycol and red iron oxide E172)
7. >5 days post standard therapy (metronidazole or vancomycin) for clinically diagnosed CDAD
8. Taking ciclosporin

* Acceptable contraceptive methods include: established use of oral, injected or implanted hormonal methods; placement of an intrauterine device (IUD) or intrauterine system (IUS); condom or occlusive cap (diaphragm or cervical/vault caps) with spermicide; true abstinence (when this is in line with the preferred and usual lifestyle of the participant); or vasectomised partner.

Exclusion criteria from 30/04/2015 to 24/02/2016:
1. Woman of childbearing potential and not willing to use at least one highly effective contraceptive method throughout the study*
2. Male with spouse/partner of childbearing potential and not willing to use condoms
3. Pregnant or breastfeeding
4. Unable to swallow tablets
5. Life expectancy of <4 weeks
6. Hypersensitivity to the active substance, to any rifamycin (e.g. rifampicin or rifabutin) or to any of its excipients (tablet core: sodium starch glycolate type A, glycerol distearate, colloidal anhydrous, silica, talc and microcrystalline cellulose. Tablet coating: hypromellose, titanium dioxide (E171), disodium edentate, propylene glycol and red iron oxide E172)
7. >5 days post standard therapy (metronidazole or vancomycin) for clinically diagnosed CDAD

* Acceptable contraceptive methods include: established use of oral, injected or implanted hormonal methods; placement of an intrauterine device (IUD) or intrauterine system (IUS); condom or occlusive cap (diaphragm or cervical/vault caps) with spermicide; true abstinence (when this is in line with the preferred and usual lifestyle of the participant); or vasectomised partner.

Original exclusion criteria:
1. Pregnant or breast feeding
2. Hypersensitivity to the active substance, to any rifamycin (e.g. rifampicin or rifabutin) or to any of its excipients (Tablet core: Sodium starch glycolate type A, glycerol distearate, colloidal anhydrous, silica, talc and microcrystalline cellulose. Tablet coating: hypromellose, titanium dioxide (E171), disodium edentate, propylene glycol and red iron oxide E172)
3. >5 days post standard therapy (metronidazole or vancomycin) for clinically diagnosed CDAD

Recruitment start date

11/12/2012

Recruitment end date

10/03/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Nottingham University Hospitals
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

King’s Mill Hospital
Sutton-in-Ashfield
NG17 4JL
United Kingdom

Trial participating centre

Royal Derby Hospital
Derby
DE22 3NE
United Kingdom

Trial participating centre

Northern General Hospital
Sheffield
S5 7AU
United Kingdom

Trial participating centre

Chesterfield Royal Hospital
Chesterfield
S44 5BL
United Kingdom

Trial participating centre

Royal Shrewsbury Hospital
Shrewsbury
SY3 8XQ
United Kingdom

Trial participating centre

County Durham and Darlington NHS Foundation Trust
Darlington
DL3 6HX
United Kingdom

Trial participating centre

Sunderland Royal Hospital
Sunderland
SR4 7TP
United Kingdom

Trial participating centre

Kettering General Hospital
Kettering
NN16 8UZ
United Kingdom

Trial participating centre

Dorset County Hospital
Dorchester
DT1 2JY
United Kingdom

Trial participating centre

James Cook Hospital
Middlesbrough
TS4 3BW
United Kingdom

Trial participating centre

North Cumbria University Hospitals
Carlisle
CA2 7HY
United Kingdom

Trial participating centre

Hampshire Hospitals NHS Foundation Trust
Basingstoke
RG24 9NA
United Kingdom

Trial participating centre

University Hospitals Southampton
Southampton,
SO16 6YD
United Kingdom

Trial participating centre

New Cross Hospital
Wolverhampton
WV10 0QP
United Kingdom

Trial participating centre

Doncaster Royal Infirmary
Doncaster
DN2 5LT
United Kingdom

Trial participating centre

Russells Hall Hospital
Dudley
DY1 2HQ
United Kingdom

Trial participating centre

Stepping Hill Hospital
Stockport
SK2 7JE
United Kingdom

Trial participating centre

Queens Hospital
Romford
RM7 0AG
United Kingdom

Trial participating centre

King’s College Hospital
London
SE5 9RS
United Kingdom

Sponsor information

Organisation

University of Nottingham (UK)

Sponsor details

Research Innovation Services
Kings Meadow Campus
Lenton Lane
Nottingham
NG7 2NR
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institute of Health Research (NIHR) (UK) - Research for Patient Benefit (RfPB) Grant Codes: PB-PG-1010-23257

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

On 24/02/2016 the recruitment end date was changed from 11/12/2015 to 10/03/2016. On 30/04/2015 the following changes were made to the trial record: 1. The overall start date was changed from 08/11/2012 to 11/12/2012. 2. The overall end date was changed from 31/12/2014 to 11/09/2016.