Condition category
Digestive System
Date applied
20/02/2017
Date assigned
08/03/2017
Last edited
09/11/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

Not Applicable

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 20 3311 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 statement:
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

Publication citations

Additional files

Editorial Notes

09/11/2017: The ISRCTN prospective/retrospective flag compares the date of registration with the recruitment start date and does not include any grace period. The registration of this study was requested through the NIHR Portfolio and was finalised within 6 months of the recruitment starting.