Rifaximin to reduce infection in decompensated cirrhosis
| ISRCTN | ISRCTN10994757 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10994757 |
| EudraCT/CTIS number | 2016-002628-96 |
| Secondary identifying numbers | 33490 |
- Submission date
- 20/02/2017
- Registration date
- 08/03/2017
- Last edited
- 30/08/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Plain English summary of protocol
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 550 mg twice a day for 6 months. Those in the second group take a placebo (dummy drug) twice a day for 6 months. At the start of the study, during treatment, after treatement and after 9 and 12 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
Contact information
Scientific
Liver & Anti Viral Unit10th Floor
QEQM
St Mary's Hospital
South Wharf Road
London
W2 1NY
United Kingdom
| Phone | +44 7415 871928 |
|---|---|
| rooshi.nathwani08@imperial.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Prevention, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | No participant information sheet available |
| Scientific title | A multi-centre, double-blind, randomised, controlled clinical trial of rifaximin to reduce infection in patients admitted to hospital with decompensated cirrhosis |
| Study acronym | R-RID |
| Study objectives | 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(s) | South West – Central Bristol Research Ethics Committee, 20/09/2016, ref: 16/SW/0232 |
| Health condition(s) or problem(s) studied | Decompensated cirrhosis |
| 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 550 mg twice a day for 6 months Control group: Participants receive placebo 550 mg twice a day for 6 months Participants in both groups are followed up for 6 months by their consultant during their routine clinic appointments. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Rifaximin |
| Primary outcome measure | 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 study start date | 15/04/2016 |
| Completion date | 30/01/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 80 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 268; UK Sample Size: 268 |
| Total final enrolment | 78 |
| Key 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. Aged 18 - 80 years |
| Key exclusion criteria | 1. C.difficile infection 2. HIV antibody positive 3. Immunosuppression (excluding low dose steroids/steroid sparing agents for AIH <20 mg 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 |
| Date of first enrolment | 12/01/2017 |
| Date of final enrolment | 31/03/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
South Wharf Road
London
W2 1NY
United Kingdom
Prescot Street
Liverpool
L7 8XP
United Kingdom
Edgbaston
Birmingham
B15 2GW
United Kingdom
Frimley
GU16 7UJ
United Kingdom
London
SW10 9NH
United Kingdom
Sponsor information
University/education
Joint Research Compliance Office
2nd Floor, Medical School Building
St Mary’s Hospital
Norfolk Place
London
W2 1NY
England
United Kingdom
| Phone | +44 20 3311 0204 |
|---|---|
| jrco.ctimp.team@imperial.ac.uk | |
"ROR" |
https://ror.org/041kmwe10 |
Funders
Funder type
Industry
No information available
No information available
Results and Publications
| Intention to publish date | 31/01/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| 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. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Thesis results | 01/06/2021 | 30/08/2023 | No | No |
Editorial Notes
30/08/2023: The following changes have been made:
1. Thesis reference added.
2. The final enrolment number has been added from the reference.
26/03/2019: The condition has been changed from "Specialty: Hepatology, Primary sub-specialty: Hepatology; UKCRC code/ Disease: Oral and Gastrointestinal/ Other diseases of the digestive system" to "Decompensated cirrhosis" following a request from the NIHR.
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.
