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Trial registered on ANZCTR


Registration number
ACTRN12617000184370
Ethics application status
Approved
Date submitted
13/01/2017
Date registered
3/02/2017
Date last updated
18/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
The Effect of Gut Sterilisation on the Prevention of Progression of Portal Hypertension in Cirrhosis.
Scientific title
The Effect of Gut Sterilisation with Rifaximin on the Prevention of Progression of Portal Hypertension in Cirrhosis.
Secondary ID [1] 290780 0
None
Universal Trial Number (UTN)
Trial acronym
N/A
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver cirrhosis 301391 0
Portal hypertension 301392 0
Variceal bleeding 301393 0
Condition category
Condition code
Oral and Gastrointestinal 301138 301138 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 296696 0
Treatment: Drugs
Comparator / control treatment
No
Control group
Uncontrolled

Outcomes
Primary outcome [1] 300552 0
Proportion of participants with a reduction in portal pressure, assessed by hepatic venous pressure gradient measurements.
Timepoint [1] 300552 0
End of treatment (6 months from baseline)
Primary outcome [2] 300633 0
Proportion of participants with a reduction in varices size and other high risk features (composite outcome), assessed by endoscopy.
Timepoint [2] 300633 0
End of treatment (6 months from baseline)
Primary outcome [3] 300634 0
Proportion of participants with a reduction in variceal bleeding, assessed by endoscopy.
Timepoint [3] 300634 0
End of treatment (6 months from baseline)
Secondary outcome [1] 330462 0
Proportion of participants with a reduction in ascites development, assessed by endoscopy.
Timepoint [1] 330462 0
12 months post-treatment completion
Secondary outcome [2] 330463 0
Alteration of gut microbiota as a result of Rifaximin use, assessed by fecal sample and duodenum and rectal biopsy samples.
Timepoint [2] 330463 0
6 months post-treatment completion
Secondary outcome [3] 330464 0
Proportion of participants with a reduction in diuretic therapy, assessed by medical records.
Timepoint [3] 330464 0
12 months post-treatment completion

Eligibility
Key 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
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
13/02/2017
Actual
Date of last participant enrolment
Anticipated
5/02/2018
Actual
Date of last data collection
Anticipated
5/02/2019
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 7187 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 7188 0
The Alfred - Prahran
Recruitment hospital [3] 7189 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 14950 0
5000 - Adelaide
Recruitment postcode(s) [2] 14951 0
3004 - Prahran
Recruitment postcode(s) [3] 14952 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 295265 0
Commercial sector/Industry
Name [1] 295265 0
Norgine Pty Ltd
Country [1] 295265 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
North Terrace, Adelaide
SA 5000
Country
Australia
Secondary sponsor category [1] 294157 0
None
Name [1] 294157 0
Address [1] 294157 0
Country [1] 294157 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296599 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 296599 0
Level 4, Women's Health Centre
Royal Adelaide Hospital
North Terrace, Adelaide
South Australia 5000
Ethics committee country [1] 296599 0
Australia
Date submitted for ethics approval [1] 296599 0
05/04/2016
Approval date [1] 296599 0
19/12/2016
Ethics approval number [1] 296599 0
HREC/16/RAH/121

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71258 0
Dr Edmund Tse
Address 71258 0
Lvl 7 OPD
Royal Adelaide Hospital
North Terrace,
Adelaide, SA 5000
Country 71258 0
Australia
Phone 71258 0
+61 8 8222 4248
Fax 71258 0
Email 71258 0
[email protected]
Contact person for public queries
Name 71259 0
Sumudu Narayana
Address 71259 0
Lvl 7 OPD
Royal Adelaide Hospital
North Terrace,
Adelaide, SA 5000
Country 71259 0
Australia
Phone 71259 0
+61 8 82224248
Fax 71259 0
Email 71259 0
[email protected]
Contact person for scientific queries
Name 71260 0
Sumudu Narayana
Address 71260 0
Lvl 7 OPD
Royal Adelaide Hospital
North Terrace,
Adelaide, SA 5000
Country 71260 0
Australia
Phone 71260 0
+61 8 82224248
Fax 71260 0
Email 71260 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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