Plain English Summary
Background and study aims
Cirrhosis is the result of long-term, continuous damage to the liver and may be due to many different causes. The damage leads to scarring, known as fibrosis. Irregular bumps (nodules) replace the smooth liver tissue and the liver becomes harder. Together, the scarring and the nodules are called cirrhosis. Cirrhosis can take many years to develop and can do so without any noticeable symptoms until the damage to the liver is very serious. The build-up of scar tissue can interfere with the flow of blood to the liver and stop it from functioning properly, eventually leading to liver failure. Patients with decompensated cirrhosis (when the liver is not working properly) are at risk of dying from life-threatening complications of liver disease, such as bleeding varices (internal bleeding); ascites (fluid in the belly); encephalopathy (confusion); and jaundice (yellowing of eyes and skin). Rifaximin is an antibiotic most often used to treat diarrhea caused by the common bacteria known as E. coli. The aim of this study is to find out whether use of Rifaximin can reduce the risk of infection in patients admitted to hospital with cirrhosis.
Who can participate?
Patients aged between 18 and 80 who have been admitted to hospital with cirrhosis.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group take Rifaximin 550mg twice a day for six months. Those in the second group take a placebo (dummy drug) twice a day for six months. At the start of the study, during treatment, after treatement and after nine and twelve months, participants have information collected about their use of antibiotics and whether they have had infections at routine clinic appointments.
What are the possible benefits and risks of participating?
There may not be any direct benefits for patients taking part in this study personally, but the care that participants receive as part of this study may reduce their risk of infection whilst they are being treated for their cirrhosis. The knowledge gained from the trial and looking at study samples in the laboratory during and after treatment may improve the treatment offered to patients with cirrhosis in the future. There aren’t any significant risks in participating in this trial. The medicine being used in this study is already licenced and is used in clinical care and is very well tolerated with minimal side effects.
Where is the study run from?
St Mary’s Hospital (lead centre) and four other NHS hospitals in England (UK)
When is the study starting and how long is it expected to run for?
April 2016 to January 2020
Who is funding the study?
1. Norgine Ltd (UK)
2. Alfa Wassermann S.P.A (Italy)
Who is the main contact?
Dr Rooshi Nathwani
rooshi.nathwani08@imperial.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Rooshi Nathwani
ORCID ID
Contact details
Liver & Anti Viral Unit10th Floor
QEQM
St Mary's Hospital
South Wharf Road
London
W2 1NY
United Kingdom
+44 7415 871928
rooshi.nathwani08@imperial.ac.uk
Additional identifiers
EudraCT number
2016-002628-96
ClinicalTrials.gov number
Protocol/serial number
33490
Study information
Scientific title
A multi-centre, double-blind, randomised, controlled clinical trial of Rifaximin to reduce infection in patients admitted to hospital with decompensated cirrhosis
Acronym
R-RID
Study hypothesis
The aim of the study is to investigate whether the use of Rifaximin reduces the risk of infection in patients admitted to hospital with cirrhosis.
Ethics approval
South West – Central Bristol Research Ethics Committee, 20/09/2016, ref: 16/SW/0232
Study design
Randomised; Interventional; Design type: Treatment, Prevention, Drug
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
No participant information sheet available
Condition
Specialty: Hepatology, Primary sub-specialty: Hepatology; UKCRC code/ Disease: Oral and Gastrointestinal/ Other diseases of the digestive system
Intervention
Patients will be randomised to one of two groups in a ratio of 1:1 using a blinded randomisation list drawn up by an Imperial statistician and InForm software.
Intervention group: Participants receive Rifaximin 550mg twice a day for six months
Control group: Participants receive Placebo 550mg twice a day for six months
Participants in both groups are followed up for six months by their Consultant during their routine clinic appointments.
Intervention type
Drug
Phase
Drug names
Rifaximin
Primary outcome measures
Incidence of secondary or recurrent infections in patients with cirrhosis during hospitalisation or after hospital discharge is assessed using clinical evaluations at baseline, 3, 7, 14, 28 and 90 days, at 6 months (EoT) and at 9 and 12 months.
Secondary outcome measures
1. Extrahepatic organ failure (e.g. renal, neurological) rate is measured by reviewing patient notes at baseline, 3, 7, 14, 28 and 90 days, at 6 months (EoT) and at 9 and 12 months
2. Mortality rate is measured by reviewing patient notes at baseline, 3, 7, 14, 28 and 90 days, at 6 months (EoT) and at 9 and 12 months
3. Readmission with sepsis rates is measured by reviewing patient notes at baseline, 3, 7, 14, 28 and 90 days, at 6 months (EoT) and at 9 and 12 months
4. Length of hospital stay is measured by reviewing patient notes at baseline, 3, 7, 14, 28 and 90 days, at 6 months (EoT) and at 9 and 12 months
Overall trial start date
15/04/2016
Overall trial end date
30/01/2020
Reason abandoned
Eligibility
Participant inclusion criteria
1. Clinical/biochemical/radiological +/- histological diagnosis of cirrhosis
2. Hospital admission with complication of cirrhosis (e.g. alcoholic hepatitis,sepsis, variceal bleeding)
3. Commencement on antimicrobial therapy
4. Age 18 - 80 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 268; UK Sample Size: 268
Participant exclusion criteria
1. C.difficile infection
2. HIV antibody positive
3. Immunosuppression (excluding low dose steroids/steroid sparing agents for AIH < 20mg or equivalent of prednisolone)
4. Advanced disseminated Hepatocellular Carcinoma or invasive carcinoma
5. eGFR < 30 on screening/randomisation
6. End-stage/severe cardiac, pulmonary or kidney disease
7. IDDM
8. Colitis or coeliac disease
9. Pregnancy
10. Already receiving Rifamixin
Recruitment start date
12/01/2017
Recruitment end date
31/03/2019
Locations
Countries of recruitment
United Kingdom
Trial participating centre
St Mary’s Hospital
Imperial College London & Imperial College Healthcare NHS Trust,
South Wharf Road
London
W2 1NY
United Kingdom
Trial participating centre
The Royal Liverpool University Hospital
Gastrointestinal and Liver Services,
Prescot Street
Liverpool
L7 8XP
United Kingdom
Trial participating centre
Queen Elizabeth Hospital Birmingham
Mindelsohn Way,
Edgbaston
Birmingham
B15 2GW
United Kingdom
Trial participating centre
Frimley Park Hospital
Portsmouth Road
Frimley
GU16 7UJ
United Kingdom
Trial participating centre
Chelsea & Westminster Hospital
369 Fulham Palace Road
London
SW10 9NH
United Kingdom
Sponsor information
Organisation
Imperial College London
Sponsor details
Joint Research Compliance Office
2nd Floor
Medical School Building
St Mary’s Hospital
Norfolk Place
London
W2 1NY
United Kingdom
+44 203 311 0204
jrco.ctimp.team@imperial.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Industry
Funder name
Norgine Ltd
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Alfa Wassermann S.P.A
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
1. Interim analysis shared with study funders, interim results to be published in peer reviewed journals, and interim results to be presented at international conferences and meetings: April – June 2018
2. Final analysis shared with study funders, final results to be published in peer reviewed journals, and final results to be presented at international conferences and meetings: January 2020
IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
31/01/2020
Participant level data
To be made available at a later date
Results - basic reporting
Publication summary