Condition category
Infections and Infestations
Date applied
22/08/2014
Date assigned
30/09/2014
Last edited
01/10/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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. We intend to find out if the same thing might be true in bilharzia of the liver. If so, we would need to carry out larger studies to see if we can reduce the frequency of bleeding attacks, with the ultimate aim in the future of reducing deaths from portal hypertension.

Who can participate?
Adults with bilharzia of the liver.

What does the study involve?
One group will receive rifaximin orally twice per day plus usual care for 42 days while the other group will not receive rifaximin but will continue on the usual care. You will 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 will be measured in blood samples. You will be asked to give blood samples at the start of the study and on day 42 and day 90. Thereafter you will be 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?
Department of Internal Medicine, University Teaching Hospital, Nationalist Road, Lusaka, 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

Trial website

Contact information

Type

Scientific

Primary contact

Dr Edford Sinkala

ORCID ID

Contact details

Department of Internal Medicine
University of Zambia School of Medicine
University Teaching Hospital
Nationalist Road
Lusaka
10101
Zambia
sinkalaeddie@yahoo.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

TROPGAN/007

Study information

Scientific title

Rifaximin in patients with portal hypertension due to schistosomiasis in Zambia: an open-label trial

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

University of Zambia Biomedical Research Ethics Committee; 21/08/2012; ref. 00-07-12

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 controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

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

Phase

Not Applicable

Drug names

Rifaximin

Primary outcome measures

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 trial start date

10/01/2014

Overall trial end date

31/12/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Oesophageal varices
2. Schistosomiasis seropositive

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

80

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

Trial participating centre

Department of Internal Medicine
Lusaka
10101
Zambia

Sponsor information

Organisation

University of Zambia (Zambia)

Sponsor details

School of Medicine
Research Support Centre
Nationalist Road
Lusaka
10101
Zambia
mkatubulushi@yahoo.co.uk

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Wellcome Trust (UK) - Southern Africa Consortium for Research Excellence (SACORE)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes