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Trial registered on ANZCTR


Registration number
ACTRN12612001026819
Ethics application status
Approved
Date submitted
19/09/2012
Date registered
24/09/2012
Date last updated
24/09/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Bacterial translocation and amelioration of liver cell damage in response to treatment with propranolol, with or without rifaximin, in patients with cirrhosis and portal hypertension
Scientific title
Bacterial translocation and amelioration of liver cell damage in response to treatment with propranolol, with or without rifaximin, in patients with cirrhosis and portal hypertension
Secondary ID [1] 281259 0
Nil
Universal Trial Number (UTN)
U1111-1134-8680
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cirrhosis and portal hypertension 287452 0
Condition category
Condition code
Oral and Gastrointestinal 287793 287793 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
All patients will be treated with oral propranolol, 40 mg thrice daily for 28 days. In patients in whom a satisfactory reduction in portal venous hypertension is not achieved at this time point, propranolol will be continued at unchanged dose and oral rifaximin, 550 mg twice daily will be added for 28 days. Patients in whom propranolol is either contraindicated or not tolerated will be treated with oral rifaximin monotherapy, 550 mg twice daily for 28 days.
Intervention code [1] 285730 0
Treatment: Drugs
Comparator / control treatment
Results in individual patients after intervention with propranolol, propranolol + rifaximin or rifaximin alone (as described above) will be compared to results in individual patients prior to intervention (standard care). Patients thus act as their own control. There is no placebo-treted group in this study.
Control group
Active

Outcomes
Primary outcome [1] 288012 0
Portal venous pressure, as assessed by direct measurement of the hepatic venous pressure gradient
Timepoint [1] 288012 0
Baseline, after 28 days of propranolol and, when reduction in portal venous hypertension is inadequate, after 28 days of combined propranolol and rifaximin.

Patients intolerant of or with contraindications to propranolol will be studied at baseline and after 28 days of rifaximin monotherapy.
Secondary outcome [1] 299285 0
Bacterial translocation/liver cell function, as assessmed by analysis of peripheral blood for bacterial DNA, innate immune activity and standard liver function tests.
Timepoint [1] 299285 0
Baseline, after 28 days of propranolol and, when reduction in portal venous hypertension is inadequate, after 28 days of combined propranolol and rifaximin.

Patients intolerant of or with contraindications to propranolol will be studied at baseline and after 28 days of rifaximin monotherapy.

Eligibility
Key inclusion criteria
Cirrhosis
Portal hypertension
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Propranolol treatment in the previous three months
Antibiotic treatment within the previous three months
Hepatocellular carcinoma
Inability to give informed consent

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)
This is a non-randomised study
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Active.

Patients will receive current standard of care, including oral propranolol 40 mg thrice daily. If therapeutic response is suboptimal (as described above), oral rifaximin will be added. Patients with contraindications to or intolerant of oral propranolol will be treated with oral rifaximin alone.
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 286029 0
Self funded/Unfunded
Name [1] 286029 0
Professor Stephen Riordan
Address [1] 286029 0
Gastrointestinal and Liver Unit
Prince of Wales Hospital
Barker Street
Randwick NSW 2031
Country [1] 286029 0
Australia
Primary sponsor type
Individual
Name
Professor Stephen Riordan
Address
Gastrointestinal and Liver Unit
Prince of Wales Hospital
Barker Street
Randwick NSW 2031
Country
Australia
Secondary sponsor category [1] 284843 0
None
Name [1] 284843 0
N/A
Address [1] 284843 0
N/A
Country [1] 284843 0
Other collaborator category [1] 277078 0
Individual
Name [1] 277078 0
Professor Denis Wakefield
Address [1] 277078 0
University of New South Wales
Kensington NSW 2052
Country [1] 277078 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288077 0
South Eastern Sydney Local Health District
Ethics committee address [1] 288077 0
Edmund Blacket Building
Prince of Wales Hospital
Cnr High and Avoca Streets
Randwick NSW 2031
Ethics committee country [1] 288077 0
Australia
Date submitted for ethics approval [1] 288077 0
Approval date [1] 288077 0
Ethics approval number [1] 288077 0

Summary
Brief summary
Measurement of the hepatic venous pressure gradient is performed in patients with cirrhosis to assess for portal hypertension and monitor effectiveness of portal venous pressure-lowering therapies. These include treatment with the non-selective beta-blocker, propranolol, while the broad-spectrum antibiotic, rifaximin, has also been shown to be effective.

Whether these treatments to reduce portal venous hypertension in patients with cirrhosis are also associated with reduced bacterial translocation from the intestine and whether reduced bacterial translocation, in turn, results in amelioration of liver dameg are currently unknown.

The aim of this study is to meaure markers of bacterial translocation and liver damage in patients with portal venous hypertension complicating cirrhosis who are undergoing hepatic venous pressure gradient measurement at baseline and after four weeks of propranolol therapy. Should the portal venous pressure not be improved satisfactorily after treatment with propranolol alone, then rifaximin will be added and the portal venous pressure and markers of bacterial translocation and liver damage will be reassessed after a further 28 days. Patients intolerant of or with contraindications to propranolol will be studied at baseline and after 28 days of rifaximin monotherapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34733 0
Address 34733 0
Country 34733 0
Phone 34733 0
Fax 34733 0
Email 34733 0
Contact person for public queries
Name 17980 0
Professor Stephen Riordan
Address 17980 0
Gastrointestinal and Liver Unit
Prince of Wales Hospital
Barker Street
Randwick NSW 2031
Country 17980 0
Australia
Phone 17980 0
+ 61 2 9382 3100
Fax 17980 0
Email 17980 0
Stephen.Riordan@@SESIAHS.HEALTH.NSW.GOV.AU
Contact person for scientific queries
Name 8908 0
Professor Stephen Riordan
Address 8908 0
Gastrointestinal and Liver Unit
Prince of Wales Hospital
Barker Street
Randwick NSW 2031
Country 8908 0
Australia
Phone 8908 0
+ 61 2 9382 3100
Fax 8908 0
Email 8908 0
Stephen.Riordan@SESIAHS.HEALTH.NSW.GOV.AU

No information has been provided regarding IPD availability
Summary results
No Results