None listed
Conditions
Brief summary
The primary purpose of this trial is to assess the effectiveness of Rifaximin in preventing variceal bleeding (bleeding from enlarged veins due to increases in blood pressure) in at risk patients and to determine the effect of Rifaximin on gut bacteria. Who is it for? You may be eligible to participate in this trial if you are aged 40 or over with compensated cirrhosis (chronic liver disease) and are at high risk of variceal bleeding. You must be unable to take propranolol (a blood pressure medication) or have declined this treatment for variceal bleeding to be eligible for this trial. You are also eligible for the trial if you have recently commenced or are continuing with endoscopic variceal ligation (EVL - is a procedure where enlarged veins in the oesophagus are tied off using a rubber band) as preventative treatment for variceal bleeding. Study details All participants enrolled in this trial will receive Rifaximin. Before treatment begins, you will need to undergo a hepatic venous pressure measurement and provide a stool sample, so that your treating team of clinicians will be able to compare portal pressure (blood pressure in the liver) before and after Rifaximin treatment and determine the effectiveness of this new treatment. Treatment period will be for 6 months, where you will have to take one Rifaximin pill (each 550mg) twice a day, with or without food, every day until the end of the treatment period. You will need to return to your doctor’s office in the middle of the treatment period (3 months) to provide a stool sample, collect your next cycle of drugs and complete standard of care treatment for your cirrhosis. At the end your treatment, you will have to return to the hospital for some follow up procedures to determine the effectiveness of the treatment drug, Rifaximin. These procedures will include a repeat hepatic venous pressure measurement, an endoscopy and a proctoscopy to observe size of varices and obtain biopsy samples, and a stool sample. The biopsy samples, a duodenal and rectal biopsy, will be obtained to determine whether Rifaximin changed gut bacteria and if this had a role in treatment outcome. Post-treatment all participants will be asked to provide a stool sample at 12 months, so that the doctor can ensure that your bacteria is back to normal. We hope that Rifaximin will provide an alternative treatment option that may be better at controlling inflammation of the liver and reducing portal pressure that results in bleeding, without the associated side effects, compared to current treatment options. It is hoped that the findings from this study will help optimise treatment management of patients with cirrhosis.
Interventions
Participants in the trial will be treated with the drug Rifaximin, to determine the efficacy of Rifaximin in reducing portal hypertension, and therefore risk of variceal bleeding, in patients with compensated cirrhosis.
Participants will take a 550mg Rifaximin tablet, orally, twice a day for a duration of 6 months (treatment length). Medication will be provided in 2 rounds (every 3 months), with adherence monitored through the return of the empty drug packet to the clinic at the end of the first
Participants in the trial will be treated with the drug Rifaximin, to determine the efficacy of Rifaximin in reducing portal hypertension, and therefore risk of variceal bleeding, in patients with compensated cirrhosis. Participants will take a 550mg Rifaximin tablet, orally, twice a day for a duration of 6 months (treatment length). Medication will be provided in 2 rounds (every 3 months), with adherence monitored through the return of the empty drug packet to the clinic at the end of the first 3 months.
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Aged 40 years and over Those with ability to give informed consent Known clinically significant portal hypertension (HVPG greater than or equal to 10mmHg) High risk varices with features: - Large oesophageal varices >5mm in diameter or - High risk features including cherry red spot or red wale Contraindication of commencement/continuing of propranolol including, - Chronic obstructive airways disease - Unstable diabetics with risk of hypoglycaemia unawareness - Intolerance to beta blockers Commenced or continuing EVL treatment Stable, compensated, persistent chronic liver diseases (predictable progression of liver fibrosis) - Ongoing regular and stable alcohol intake - Persistent viral hepatitis (a) Hepatitis B controlled on treatment or immune control phase of infection (b) Hepatitis C with prior clearance, > 12 months ago - Ongoing metabolic liver disease such as NAFLD
Exclusion criteria
Significant renal impairment and unable to safely tolerate intravenous contrast Ischaemic heart disease or congestive cardiac failure Previous possible allergy to Rifaximin, related Rifamycin antibiotics, or any of the other ingredients in Rifaximin, by the patient Causes that lead to unstable liver disease progression and/or likely reversible portal hypertension (Onset >1 month from the time of diagnosis of high risk varices or during the study): - Portal vein thrombosis - Child Pugh B or greater - Flare of chronic hepatitis - Hepatitis C treatment in the last 12 months - Significant change in alcohol intake ( >4 standard drinks) Concurrent diagnosis of hepatocellular cancer Pregnant or breastfeeding women Creatinine clearance of less than 60 mls/min Platelet count of less than 80,000/mm3 Those whom investigators believe are unlikely to have more than 12 month’s life expectancy
Outcome results
None listed