Rifaximin in patients with portal hypertension due to schistosomiasis in Zambia
| ISRCTN | ISRCTN67590499 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN67590499 |
| Secondary identifying numbers | TROPGAN/007 |
- Submission date
- 22/08/2014
- Registration date
- 30/09/2014
- Last edited
- 24/01/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
There is a form of Bilharzia (a parasite) that affects the liver and is prevalent in the tropical countries. Parts of Zambia are severely affected with this disease. Long-standing bilharzia in the liver can lead to increased blood pressure in the portal vein (portal hypertension), which connects the intestine to the liver. This leads to accumulation of scar tissue in the liver and then dilated blood vessels in the food pipe. When these bleed, the blood loss into the stomach can be fatal; this is a common cause of hospital admission in Zambia. We know that both scarring of liver substance (known as cirrhosis) and bilharzia affecting the liver can cause portal hypertension. These two diseases are similar. The major difference is that in bilharzia affecting the liver, there is scarring around blood vessels (periportal fibrosis) and the function remains normal, while in liver cirrhosis there is involvement of liver substance and the liver function is affected depending on the how much of the liver is damaged. In cirrhosis, bacteria leaking out of the bowels into the blood circulation is associated with increased portal pressure and is the major cause of hospital admissions and death. It is not clear whether the leaking out of bacteria from the bowels into the blood circulation occurs in patients with bilharzia of the liver in the same way as in cirrhosis. We set out to study this problem in patients affected with bilharzia by using rifaximin. Rifaximin is a drug that is given by mouth and it acts locally on bacteria in the bowels as it is not significantly absorbed. We suggest that giving it orally may lead to a reduction in markers that measure the evidence of bacteria leaking from the bowels, hence suggesting that the leakage occurs in these patients. Use of antibiotics to prevent leakage of bacteria into the bloodstream from the bowels has shown a lot of benefit in cirrhosis by reducing portal vein pressure. The aim is to find out if the same thing might be true in bilharzia of the liver.
Who can participate?
Adults with bilharzia of the liver
What does the study involve?
One group receive rifaximin orally twice per day plus usual care for 42 days while the other group do not receive rifaximin but continue on the usual care. You have to take the tablets once per day. In addition to checking markers that measure leakage of bacteria into the bloodstream, we are going to measure other markers that indicate inflammation and those that measure scarring of the liver. These markers are measured in blood samples. You are asked to give blood samples at the start of the study and on day 42 and day 90. Thereafter you are followed up for another 3 months.
What are the possible benefits and risks of participating?
Patients may benefit from close monitoring of the disease. Risks include discomfort from the needle prick when drawing blood and side effects of rifaximin, which could include headache, dizziness, bloating of tummy, constipation, diarrhea and fever; however, these are uncommon and non-specific.
Where is the study run from?
University of Zambia (Zambia)
When is the study starting and how long is it expected to run for?
January 2014 to December 2015
Who is funding the study?
The Wellcome Trust (UK)
Who is the main contact?
Dr Edford Sinkala
sinkalaeddie@yahoo.com
Contact information
Scientific
Department of Internal Medicine
University of Zambia School of Medicine
University Teaching Hospital
Nationalist Road
Lusaka
10101
Zambia
| sinkalaeddie@yahoo.com |
Study information
| Study design | Open-label rifaximin given to patients in one arm and usual care only given to patients in the other arm |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Rifaximin in patients with portal hypertension due to schistosomiasis in Zambia: an open-label trial |
| Study acronym | RFX-SCHISTO |
| Study hypothesis | One of the two major forms of schistosomiasis leads to portal hypertension and then oesophageal varices. We have laboratory evidence that, in a way similar to cirrhosis, bacterial translocation may exacerbate the problem and drive disease progression. This trial is intended to explore the hypothesis that rifaximin may reduce markers of microbial translocation, fibrosis, and inflammation in patients with schistosomiasis mansoni-related portal hypertension in Zambia. |
| Ethics approval(s) | University of Zambia Biomedical Research Ethics Committee, 21/08/2012, ref: 00-07-12 |
| Condition | Schistosomiasis, oesophageal varices, portal hypertension |
| Intervention | One group of 40 Zambian adults with bilharzia of the liver in addition to receiving standard care will receive rifaximin 600 mg orally twice per day for 42 days while the other group will not receive rifaximin but will continue on the usual standard care. Standard care includes being treated for schistosomiasis with praziquantel and receiving long-term beta blockers (e.g., propranolol) to prevent variceal bleeding. In some instances variceal banding is done as part of standard care. In addition to checking markers that measure leakage of bacteria into the bloodstream, we are going to measure other markers that indicate inflammation and those that measure scarring of the liver. These markers will be measured in blood samples. These patients will be asked to give blood samples on days 0, 42 and 90 during routine follow-up visits. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Rifaximin |
| Primary outcome measure | Changes in markers of translocation |
| Secondary outcome measures | 1. Changes in markers of fibrosis 2. Changes in inflammatory markers 3. Re-bleeding episodes 4. Death Baseline information will be captured using a questionnaire and blood will be collected for baseline markers of translocation, fibrosis and inflammation. These will be measured using ELISA. Then these patients will be followed up on day 42, day 90 and thereafter for 3 months, making a total of 6 months. At each visit the questionnaire will be administered and blood will be collected for the above assays |
| Overall study start date | 10/01/2014 |
| Overall study end date | 31/08/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 80 |
| Participant inclusion criteria | 1. Oesophageal varices 2. Schistosomiasis seropositive |
| Participant exclusion criteria | 1. HIV seropositive 2. Cirrhosis 3. Hepatitis virus B or C infection |
| Recruitment start date | 10/01/2014 |
| Recruitment end date | 31/12/2015 |
Locations
Countries of recruitment
- Zambia
Study participating centre
10101
Zambia
Sponsor information
University/education
School of Medicine
Research Support Centre
Nationalist Road
Lusaka
10101
Zambia
| mkatubulushi@yahoo.co.uk | |
"ROR" |
https://ror.org/03gh19d69 |
Funders
Funder type
Charity
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/04/2018 | 24/01/2019 | Yes | No |
Editorial Notes
24/01/2019: Publication reference added
17/01/2017: The overall trial end date was changed from 31/12/2015 to 31/08/2016.
