ANZCTR - Registration

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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]

None

Universal Trial Number (UTN)

Trial acronym

N/A

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Liver cirrhosis

Portal hypertension

Variceal bleeding

Condition category

Condition code

Oral and Gastrointestinal

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]

Treatment: Drugs

Comparator / control treatment

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Proportion of participants with a reduction in portal pressure, assessed by hepatic venous pressure gradient measurements.

Timepoint [1]

End of treatment (6 months from baseline)

Primary outcome [2]

Proportion of participants with a reduction in varices size and other high risk features (composite outcome), assessed by endoscopy.

Timepoint [2]

End of treatment (6 months from baseline)

Primary outcome [3]

Proportion of participants with a reduction in variceal bleeding, assessed by endoscopy.

Timepoint [3]

End of treatment (6 months from baseline)

Secondary outcome [1]

Proportion of participants with a reduction in ascites development, assessed by endoscopy.

Timepoint [1]

12 months post-treatment completion

Secondary outcome [2]

Alteration of gut microbiota as a result of Rifaximin use, assessed by fecal sample and duodenum and rectal biopsy samples.

Timepoint [2]

6 months post-treatment completion

Secondary outcome [3]

Proportion of participants with a reduction in diuretic therapy, assessed by medical records.

Timepoint [3]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

SA,VIC

Recruitment hospital [1]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [2]

The Alfred - Prahran

Recruitment hospital [3]

Royal Melbourne Hospital - City campus - Parkville

Recruitment postcode(s) [1]

5000 - Adelaide

Recruitment postcode(s) [2]

3004 - Prahran

Recruitment postcode(s) [3]

3050 - Parkville

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Norgine Pty Ltd

Address [1]

3/14 Rodborough Rd,
Frenchs Forest NSW 2086

Country [1]

Australia

Primary sponsor type

Hospital

Name

Royal Adelaide Hospital

Address

North Terrace, Adelaide
SA 5000

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Adelaide Hospital Research Ethics Committee

Ethics committee address [1]

Level 4, Women's Health Centre
Royal Adelaide Hospital
North Terrace, Adelaide
South Australia 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

05/04/2016

Approval date [1]

19/12/2016

Ethics approval number [1]

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

Dr Edmund Tse

Address

Lvl 7 OPD
Royal Adelaide Hospital
North Terrace,
Adelaide, SA 5000

Country

Australia

Phone

+61 8 8222 4248

Fax

edmund.tse@sa.gov.au

Contact person for public queries

Name

Sumudu Narayana

Address

Lvl 7 OPD
Royal Adelaide Hospital
North Terrace,
Adelaide, SA 5000

Country

Australia

Phone

+61 8 82224248

Fax

sumudu.narayana@sa.gov.au

Contact person for scientific queries

Name

Sumudu Narayana

Address

Lvl 7 OPD
Royal Adelaide Hospital
North Terrace,
Adelaide, SA 5000

Country

Australia

Phone

+61 8 82224248

Fax

sumudu.narayana@gmail.com

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

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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