Liver CirrhosisPhase 4RIFSYSNCT02019784
Randomised Controlled Trial of Mechanistic Effects of Rifaximin in Cirrhosis and Chronic Hepatic Encephalopathy
A Phase 4 study testing Rifaximin-α in people with Liver Cirrhosis and Hepatoencephalopathy, Early Fatal Progressive, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
Trial summary
Patients with cirrhosis are particularly prone to infection which is frequently a precipitant of hepatic encephalopathy, renal failure and circulatory collapse. Bacterial infections are of particular concern in patients with cirrhosis because they are poorly tolerated. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Cirrhosis, Hepatoencephalopathy, Early Fatal Progressive
- What is being tested?
- Rifaximin-α
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2015to Oct 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with established cirrhosis complicated by hepatic encephalopathy
- For the purposes of this study a patient will be considered to have cirrhosis if they fulfil two out of the three diagnostic criteria of confirmatory liver histology, biochemistry and/or radiologic findings consistent with cirrhosis/portal hypertension, and
- are presenting with chronic persistent overt hepatic encephalopathy (≥ grade 1) or with ≥2 episodes of overt hepatic encephalopathy in the previous 6 months.
Who cannot join
- Age ≤18 or ≥75.
- Evidence of disseminated malignancy.
- Known coeliac or inflammatory bowel disease.
- Evidence of intestinal failure, intestinal obstruction and / or previous bowel resection.
- Pre-existing immunosuppressive states including HIV infection and chronic granulomatous diseases.
- Anti-inflammatory drug use e.g non-steroidals and immunomodulatory drug use e.g. prednisolone and azathioprine.
Show all 10Show fewer
- Known hypersensitivity to rifaximin or rifamycin-derivatives
- Already receiving concomitant oral or parenteral antibiotic therapy e.g norfloxacin.
- Infection with clostridium difficile or stool testing positive for clostridium difficile toxin in the previous 3 months.
- Pregnancy or breast feeding women
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
King's College Hospital NHS Foundation Trust
London, London, SE5 9RS
About this study
Official title: A Placebo Controlled Single Centre Double Blind Randomised Trial to Investigate the Efficacy of Rifaximin Versus Placebo in Improving Systemic Inflammation and Neutrophil Malfunction in Patients With Cirrhosis and Chronic Hepatic Encephalopathy
Patients with cirrhosis are particularly prone to infection which is frequently a precipitant of hepatic encephalopathy, renal failure and circulatory collapse. Bacterial infections are of particular concern in patients with cirrhosis because they are poorly tolerated. Sepsis and associated endotoxaemia whereby bacteria produce inflammatory particles occur in approximately 40% of hospitalized patients with cirrhosis and is a major cause of death.
Gut-derived and blood-borne pathogens can induce an inflammatory response within the liver and spleen, which are the major organs that remove bacteria and their endotoxin (such as lipopolysaccharide - LPS and bacterial DNA itself) from the bloodstream. Several mechanisms have been identified and proposed in this process which depends upon a balance between the barrier functions of the gut and the 'detoxifying' capacity of the liver. People with established liver cirrhosis have been shown to have escape of endotoxin into the bloodstream produced by bacteria that reside in their intestines, which becomes more permeable or 'leaky'.
Read more
Gut dysfunction is defined by changes in the types of bacteria within the gut and in overall permeability allowing bacterial products which would otherwise be contained within the gut to travel into the bloodstream and lymphatic system with detrimental effects elsewhere in the body. This passage of bacterial products is termed bacterial translocation, and it's effects on the liver and general immune system can be then be measured.
It has now become recognised that certain types of white blood cells such as neutrophils and monocytes become dysfunctional and this predisposes to infection and may also have a more direct pathogenic role in hepatic encephalopathy. Thus neutrophil and monocytes may be a novel pharmacotherapeutic target in a condition where current therapies such as bowel aperients (e.g. lactulose) are inadequate. A therapeutic strategy utilising Rifaximin, a non-absorbable antibiotic, to modulate gut bacterial which produce ammonia, a chemical known to be important in the cause of hepatic encephalopathy, could potentially lower gut-derived systemic inflammation, endotoxaemia, infection and organ dysfunction in this population improving outcomes and prolonging transplant-free survival.
We therefore plan to test if Rifaximin positively affects markers of immune dysfunction in patients with liver cirrhosis experiencing chronic hepatic encephalopathy after 30 days of treatment, as our primary research question.
Positive results from this study would support further trials into the potential benefit of using Rifaximin to improve immune function, as well as reduce the recurrence of hepatic encephalopathy, in patients with liver cirrhosis.
Read the detailed description
Overview
The study will be designed and conducted as a double blind placebo controlled randomised controlled trial - Clinical Trial of an Investigational Medicinal Product.
This study will be performed on patients referred to King's Liver Unit for further assessment and management of chronic overt hepatic encephalopathy (≥ Grade 1) or with ≥2 episodes of overt hepatic encephalopathy in the previous 6 months.
The study will be performed on 50 patients with cirrhosis and chronic hepatic encephalopathy [25 Rifaximin and 25 placebo] aged between 18 and 75 years managed within the Liver Unit at King's College Hospital which is the largest tertiary Liver Transplant Centre within the UK. For the purposes of this study a patient will be considered to have cirrhosis if they fulfil 2 out of 3 diagnostic criteria of confirmatory liver histology, biochemistry and/or radiologic findings consistent with cirrhosis/portal hypertension, and are presenting with chronic persistent overt hepatic encephalopathy (≥ grade 1) or with ≥2 episodes of overt hepatic encephalopathy in the previous 6 months.
Patient demographics, clinical details (including Westhaven hepatic encephalopathy grade) and blood haematology, biochemistry (including venous ammonia), microbiology data and neutrophil function will be assessed and collated at baseline and following 30 and 90 days of Rifaximin therapy or placebo. Intestinal permeability will be assessed using the intestinal disaccharide test. Faecal microbiota analysis will be performed by deep pyrosequencing techniques and plasma endotoxemia will be measured (lipopolysaccharide levels) with bacterial DNA quantification as a marker of bacterial translocation. These will all be measured at 3 time points: baseline and at 30 and 90 days after initiation of Rifaximin therapy or matching placebo.
Investigations
Patients will undergo intestinal functional tests within 7 days of recruitment, whereby they will be administered a test solution of not more than a cupful (150mls) of different types of non-absorbable sugars, which are drunk in liquid form by the participants. Prior to ingestion, baseline samples will be obtained as follows:
- blood samples - for analysis of intestinal \& immune (dys)function, and metabonomic analysis ii) urine sample - for intestinal (dys)function \& metabonomic analysis iii) stool sample - for faecal biomarker and microbiota analysis
1v) ascitic sample (if clinically indicated) - surplus fluid will be analysed for bacterial translocation and immune (dys)function
Once the test solution has been ingested, blood samples will be obtained via a cannula which is placed in a vein, usually in the arm, prior to the start of the test, to allow further sampling without causing discomfort to the patient. A total of 15 samples will be obtained over a 5 hour period, with intervals ranging between 20-30mins, of not more than 6mls per sample. At the end of the test, at a 5 hour interval, a further urine sample will be collected to allow for intestinal functional testing. This is exactly the same procedure as that specified in the approved 'The Gut-Liver Axis in Liver Disease \& Liver Transplantation' study (REC ref: 12/LO/1417).
Where participants are undergoing sampling of ascitic fluid for clinical reasons any fluid in excess of pathology's requirements will be analysed along with peripheral blood samples. Ascitic samples will only be taken from patients in whom a decision has been made to take these samples for clinical reasons (this decision will not be that of the investigator). No increased volume of such sample would be required.
Clinical outcomes (development of recurrent overt hepatic encephalopathy, organ failure and infection) will be recorded for a total of 90 days.
Analysis of samples - sites
Blood, urine and ascitic samples will be analysed in the Institute of Liver Studies and King's College Hospital laboratories where various tests to determine intestinal and immune function will be undertaken. Stool samples will be analysed both at laboratories at King's College Hospital and at the Franklin-Wilkins Building, King's College London, where faecal biomarkers and faecal microbiota analyses will be performed, respectively. Metabolic analyses for metabonomic profiling will be carried out at Imperial College London (both at St Mary's Hospital and at the South Kensington Campus).
Protocol
A more detailed list of the tests and analyses to be performed is to be found in the protocol. Study-specific flow charts have also been provided for a step-by-step representation of the study, visually representing the study process including participant recruitment, randomisation, sampling protocols and analyses at the three time points and follow-up visits.
- Being tested
- Rifaximin-α, Placebo Oral Tablet
- Keywords
- Cirrhosis, Hepatic encephalopathy
- Medical subject headings
- Liver Cirrhosis, Combined Oxidative Phosphorylation Deficiency 1, Fibrosis, Hepatic Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rifaximin-αDrug
Also called Targaxan (brand name)
Rifaximin-α will be compared to placebo with the various outcome measures assessed at baseline (pre-randomisation), and then at 30 days and 90 days.
Placebo Oral TabletDrug
Placebo Oral Tablet
| Study group | Role | What they receive |
|---|---|---|
| Rifaximin-α | Active comparator | Rifaximin-α (TARGAXAN TM, manufactured by Alfa-Wasserman, Bologna, Italy) tablets - 550mg twice daily for 90 days Receives: Drug: Rifaximin-α |
| Placebo | Placebo comparator | Placebo tablets - 550mg twice daily for 90 days Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rifaximin-α reducing neutrophil spontaneous oxidative burst ex vivo
To test whether there is a reduction in spontaneous neutrophil oxidative burst of 50% compared to baseline (as measured by the Burstest which measures the spontaneous production of reactive oxygen species) 30 days following the start of rifaximin-α/placebo therapy.
Measured: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
Secondary outcomes (6)
Neutrophil bacteriocidal capacity
An improvement in neutrophil bacteriocidal capacity as measured by the Phagotest which utilises opsonised E. coli at 30 and 90 days
Measured: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
Reduction in systemic inflammation
A reduction in systemic inflammation as measured by plasma endotoxemia, bacterial DNA quantification and plasma pro-inflammatory cytokine profile at 90 days.
Measured: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
Improvement in neutrophil phenotype and function
An improvement in neutrophil phenotype and function including baseline and LPS-induced toll-like receptor 4 expression and intracellular cytokine production at 30 and 90 days.
Measured: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
Alterations in faecal microbiota at 90 days
Measured: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
Reduction in intestinal permeability and changes in faecal biomarkers (calprotectin) at 90 days.
Measured: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
Changes in urinary and plasma metabonomic profile
Changes in urinary and plasma metabonomic profile as measured by proton MR spectroscopy at 90 days
Measured: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2013 (estimated)
- Study startJan 2015
- Primary completionJun 2016
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- More trials run by King's College Hospital NHS TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- King's College London
- Responsible party
- Sponsor
- Investigators
- Debbie Shawcross, MBBS PhD, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02019784
- Sponsor's protocol ID
- KCH14-183_RIFSYS_V4.0
- Other IDs
- 2013-004708-20
- Acronym
- RIFSYS
- Status last verified
- Nov 2016
- First submitted
- 18 Dec 2013
- Last updated
- 11 Nov 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Zacharias HD, Kamel F, Tan J, Kimer N, Gluud LL, Morgan MY. Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2023 Jul 19;7(7):CD011585. doi: 10.1002/14651858.CD011585.pub2.
PubMed 37467180Patel VC, Lee S, McPhail MJW, Da Silva K, Guilly S, Zamalloa A, Witherden E, Stoy S, Manakkat Vijay GK, Pons N, Galleron N, Huang X, Gencer S, Coen M, Tranah TH, Wendon JA, Bruce KD, Le Chatelier E, Ehrlich SD, Edwards LA, Shoaie S, Shawcross DL. Rifaximin-alpha reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy: RIFSYS randomised controlled trial. J Hepatol. 2022 Feb;76(2):332-342. doi: 10.1016/j.jhep.2021.09.010. Epub 2021 Sep 24.
PubMed 34571050
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo Controlled Single Centre Double Blind Randomised Trial to Investigate the Efficacy of Rifaximin Versus Placebo in Improving Systemic Inflammation and Neutrophil Malfunction in Patients With Cirrhosis and Chronic Hepatic Encephalopathy
- ClinicalTrials.gov ID
- NCT02019784
- Acronym / sponsor ID
- RIFSYS / KCH14-183_RIFSYS_V4.0
- Keywords
- Cirrhosis, Hepatic encephalopathy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Collaborators
- King's College London
- Study start
- Jan 2015
- Primary completion
- Jun 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 24 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with cirrhosis are particularly prone to infection which is frequently a precipitant of hepatic encephalopathy, renal failure and circulatory collapse. Bacterial infections are of particular concern in patients with cirrhosis because they are poorly tolerated. Sepsis and associated endotoxaemia whereby bacteria produce inflammatory particles occur in approximately 40% of hospitalized patients with cirrhosis and is a major cause of death.
Gut-derived and blood-borne pathogens can induce an inflammatory response within the liver and spleen, which are the major organs that remove bacteria and their endotoxin (such as lipopolysaccharide - LPS and bacterial DNA itself) from the bloodstream. Several mechanisms have been identified and proposed in this process which depends upon a balance between the barrier functions of the gut and the 'detoxifying' capacity of the liver. People with established liver cirrhosis have been shown to have escape of endotoxin into the bloodstream produced by bacteria that reside in their intestines, which becomes more permeable or 'leaky'.
Gut dysfunction is defined by changes in the types of bacteria within the gut and in overall permeability allowing bacterial products which would otherwise be contained within the gut to travel into the bloodstream and lymphatic system with detrimental effects elsewhere in the body. This passage of bacterial products is termed bacterial translocation, and it's effects on the liver and general immune system can be then be measured.
It has now become recognised that certain types of white blood cells such as neutrophils and monocytes become dysfunctional and this predisposes to infection and may also have a more direct pathogenic role in hepatic encephalopathy. Thus neutrophil and monocytes may be a novel pharmacotherapeutic target in a condition where current therapies such as bowel aperients (e.g. lactulose) are inadequate. A therapeutic strategy utilising Rifaximin, a non-absorbable antibiotic, to modulate gut bacterial which produce ammonia, a chemical known to be important in the cause of hepatic encephalopathy, could potentially lower gut-derived systemic inflammation, endotoxaemia, infection and organ dysfunction in this population improving outcomes and prolonging transplant-free survival.
We therefore plan to test if Rifaximin positively affects markers of immune dysfunction in patients with liver cirrhosis experiencing chronic hepatic encephalopathy after 30 days of treatment, as our primary research question.
Positive results from this study would support further trials into the potential benefit of using Rifaximin to improve immune function, as well as reduce the recurrence of hepatic encephalopathy, in patients with liver cirrhosis.
Detailed description
Overview
The study will be designed and conducted as a double blind placebo controlled randomised controlled trial - Clinical Trial of an Investigational Medicinal Product.
This study will be performed on patients referred to King's Liver Unit for further assessment and management of chronic overt hepatic encephalopathy (≥ Grade 1) or with ≥2 episodes of overt hepatic encephalopathy in the previous 6 months.
The study will be performed on 50 patients with cirrhosis and chronic hepatic encephalopathy [25 Rifaximin and 25 placebo] aged between 18 and 75 years managed within the Liver Unit at King's College Hospital which is the largest tertiary Liver Transplant Centre within the UK. For the purposes of this study a patient will be considered to have cirrhosis if they fulfil 2 out of 3 diagnostic criteria of confirmatory liver histology, biochemistry and/or radiologic findings consistent with cirrhosis/portal hypertension, and are presenting with chronic persistent overt hepatic encephalopathy (≥ grade 1) or with ≥2 episodes of overt hepatic encephalopathy in the previous 6 months.
Patient demographics, clinical details (including Westhaven hepatic encephalopathy grade) and blood haematology, biochemistry (including venous ammonia), microbiology data and neutrophil function will be assessed and collated at baseline and following 30 and 90 days of Rifaximin therapy or placebo. Intestinal permeability will be assessed using the intestinal disaccharide test. Faecal microbiota analysis will be performed by deep pyrosequencing techniques and plasma endotoxemia will be measured (lipopolysaccharide levels) with bacterial DNA quantification as a marker of bacterial translocation. These will all be measured at 3 time points: baseline and at 30 and 90 days after initiation of Rifaximin therapy or matching placebo.
Investigations
Patients will undergo intestinal functional tests within 7 days of recruitment, whereby they will be administered a test solution of not more than a cupful (150mls) of different types of non-absorbable sugars, which are drunk in liquid form by the participants. Prior to ingestion, baseline samples will be obtained as follows:
- blood samples - for analysis of intestinal \& immune (dys)function, and metabonomic analysis ii) urine sample - for intestinal (dys)function \& metabonomic analysis iii) stool sample - for faecal biomarker and microbiota analysis
1v) ascitic sample (if clinically indicated) - surplus fluid will be analysed for bacterial translocation and immune (dys)function
Once the test solution has been ingested, blood samples will be obtained via a cannula which is placed in a vein, usually in the arm, prior to the start of the test, to allow further sampling without causing discomfort to the patient. A total of 15 samples will be obtained over a 5 hour period, with intervals ranging between 20-30mins, of not more than 6mls per sample. At the end of the test, at a 5 hour interval, a further urine sample will be collected to allow for intestinal functional testing. This is exactly the same procedure as that specified in the approved 'The Gut-Liver Axis in Liver Disease \& Liver Transplantation' study (REC ref: 12/LO/1417).
Where participants are undergoing sampling of ascitic fluid for clinical reasons any fluid in excess of pathology's requirements will be analysed along with peripheral blood samples. Ascitic samples will only be taken from patients in whom a decision has been made to take these samples for clinical reasons (this decision will not be that of the investigator). No increased volume of such sample would be required.
Clinical outcomes (development of recurrent overt hepatic encephalopathy, organ failure and infection) will be recorded for a total of 90 days.
Analysis of samples - sites
Blood, urine and ascitic samples will be analysed in the Institute of Liver Studies and King's College Hospital laboratories where various tests to determine intestinal and immune function will be undertaken. Stool samples will be analysed both at laboratories at King's College Hospital and at the Franklin-Wilkins Building, King's College London, where faecal biomarkers and faecal microbiota analyses will be performed, respectively. Metabolic analyses for metabonomic profiling will be carried out at Imperial College London (both at St Mary's Hospital and at the South Kensington Campus).
Protocol
A more detailed list of the tests and analyses to be performed is to be found in the protocol. Study-specific flow charts have also been provided for a step-by-step representation of the study, visually representing the study process including participant recruitment, randomisation, sampling protocols and analyses at the three time points and follow-up visits.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rifaximin-α | Active comparator | Drug: Rifaximin-αRifaximin-α (TARGAXAN TM, manufactured by Alfa-Wasserman, Bologna, Italy) tablets - 550mg twice daily for 90 days |
| Placebo | Placebo comparator | Drug: Placebo Oral TabletPlacebo tablets - 550mg twice daily for 90 days |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with established cirrhosis complicated by hepatic encephalopathy
- For the purposes of this study a patient will be considered to have cirrhosis if they fulfil two out of the three diagnostic criteria of confirmatory liver histology, biochemistry and/or radiologic findings consistent with cirrhosis/portal hypertension, and
- are presenting with chronic persistent overt hepatic encephalopathy (≥ grade 1) or with ≥2 episodes of overt hepatic encephalopathy in the previous 6 months.
Key exclusion criteria (10 listed)
- Age ≤18 or ≥75.
- Evidence of disseminated malignancy.
- Known coeliac or inflammatory bowel disease.
- Evidence of intestinal failure, intestinal obstruction and / or previous bowel resection.
- Pre-existing immunosuppressive states including HIV infection and chronic granulomatous diseases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rifaximin-αAlso: Targaxan (brand name)Rifaximin-α will be compared to placebo with the various outcome measures assessed at baseline (pre-randomisation), and then at 30 days and 90 days. | Drug | Rifaximin-α |
| Placebo Oral TabletPlacebo Oral Tablet | Drug | Placebo |
Primary outcome
Rifaximin-α reducing neutrophil spontaneous oxidative burst ex vivo
Time frame: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
To test whether there is a reduction in spontaneous neutrophil oxidative burst of 50% compared to baseline (as measured by the Burstest which measures the spontaneous production of reactive oxygen species) 30 days following the start of rifaximin-α/placebo therapy.
6 secondary outcomes
Neutrophil bacteriocidal capacity
Time frame: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
Reduction in systemic inflammation
Time frame: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
Improvement in neutrophil phenotype and function
Time frame: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
Alterations in faecal microbiota at 90 days
Time frame: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
Reduction in intestinal permeability and changes in faecal biomarkers (calprotectin) at 90 days.
Time frame: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
Changes in urinary and plasma metabonomic profile
Time frame: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2016.
- Derived from this study: PubMed 37467180Zacharias HD, Kamel F, Tan J, Kimer N, Gluud LL, Morgan MY. Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2023 Jul 19;7(7):CD011585. doi: 10.1002/14651858.CD011585.pub2.
- Derived from this study: PubMed 34571050Patel VC, Lee S, McPhail MJW, Da Silva K, Guilly S, Zamalloa A, Witherden E, Stoy S, Manakkat Vijay GK, Pons N, Galleron N, Huang X, Gencer S, Coen M, Tranah TH, Wendon JA, Bruce KD, Le Chatelier E, Ehrlich SD, Edwards LA, Shoaie S, Shawcross DL. Rifaximin-alpha reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy: RIFSYS randomised controlled trial. J Hepatol. 2022 Feb;76(2):332-342. doi: 10.1016/j.jhep.2021.09.010. Epub 2021 Sep 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Debbie Shawcross, MBBS PhD principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rifaximin-α in people with Liver Cirrhosis and Hepatoencephalopathy, Early Fatal Progressive, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rifaximin-α reducing neutrophil spontaneous oxidative burst ex vivo (time frame: Three time points: baseline before commencement of active drug/placebo, at 30 days and at 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02019784, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2016.