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Trial registered on ANZCTR


Registration number
ACTRN12609000381280
Ethics application status
Not yet submitted
Date submitted
8/05/2009
Date registered
28/05/2009
Date last updated
28/05/2009
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of non invasive evaluation of liver fibrosis in patients with Hepatitis B Virus(HBV) monoinfection using Fibroscan (Transient Elastography)
Scientific title
A study of non invasive evaluation of liver fibrosis in patients with Hepatitis B Virus (HBV) monoinfection using Fibroscan (Transient Elastography)
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B Virus (HBV) 4688 0
Condition category
Condition code
Oral and Gastrointestinal 237074 237074 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 participants recruited in the study will have had a liver biopsy as part of their routine standard of care in the past 3 months. Liver biopsy is considered the gold standard in determining the stage of liver disease.Transient elastography and a serum fibrosis marker(hepascore) will be evaluated against biopsy results. Transient elastography(T.E)- liver stiffness which equates to liver fibrosis will be measured using T.E. T.E is an ultrasound like device which is placed over the liver and sends a vibration through the liver.The quicker the vibration passes through the liver the more fibrosed (or stiff) the liver is. It is a painless procedure lasting 10 minutes approximately.There are no associated adverse events.A total of 3 fibroscan sessions will take place on each patient.The first at baseline(within 4 weeks of liver biopsy) then at 12 months,then at 24months. Readings are measured in kilopascals.
Blood samples will be taken first at baseline then at 12 months,then at 24months for hepascore, a serum fibrosis marker. Hepascore results will be correlated with liver biopsy result at baseline and then monitored over the 24 month period for alteration.
According to best practice participants may be commenced on antiviral medications if indicated by their liver biopsy (standard of care). These oral medications will include tenofovir,lamivudine,entecavir and adefovir as is common practice. The decision to start medication and which medication to start will be in no way influenced by the study.At the 12 and 24 month period we compare fibroscan and serum fibrosis markers among the various medication groups(if any).
Intervention code [1] 4514 0
Early detection / Screening
Comparator / control treatment
Liver biopsy
Control group
Active

Outcomes
Primary outcome [1] 5844 0
To prospectively evaluate the impact of antiviral therapy over time on progression of liver fibrosis using Fibroscan and serum markers of liver fibrosis in patients with chronic hepatitis B. Patients who go on to treatment with oral anti-viral agents will be followed 12 monthly for two years with annual Fibroscan, liver function tests, Aspartate Transaminase (AST), full blood examination, total cholesterol and Hepascore test to estimate the progression of fibrosis over time and the relationship of this to antiviral therapy.
Timepoint [1] 5844 0
At baseline, 12 and 24 months from recruitment.
Primary outcome [2] 5911 0
To evaluate the accuracy of fibroscan and non-invasive serum markers for the diagnosis of liver fibrosis when compared to liver biopsy in individuals with Hepatitis B. Fibroscan categorises liver fibrosis according to Kilopascal (Kpa) score(F0-1<7.5,F2 >7.5 <9.5 ,F3 >9.5 <13.5,F4>13.5),where F is the stage of fibrosis. These readings equate to the metavir(F) liver biopsy grading system.Using liver biopsy as the gold standard results will be compared to assess for accuracy of fibroscan for predicting liver fibrosis.Serum fibrosis markers will be assessed in a similiar manner.Using sensitivity and specificity we will attempt to validate these non invasive techniques using Area Under the Reicever operator curves.
Timepoint [2] 5911 0
This outcome will be measured at baseline only.
Secondary outcome [1] 241966 0
To prospectively evaluate the effect of insulin resistance on liver fibrosis in patients with chronic hepatitis B.
At the time time of initial fibroscan fasting serum insulin and glucose will be taken to establish the presence or absence of insulin resistance. This result will be correlated with degree of liver fibrosis
Timepoint [1] 241966 0
This outcome will be measured at baseline only.

Eligibility
Key inclusion criteria
Chronic hepatitis B infection.
Subjects having a liver biopsy as part of routine standard of clinical care.
Body mass index < 36.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Co-infection with Human Immunodeficiency Virus(HIV), HepatitisC Virus(HCV), or Hepatitis D Virus (HDV).
Evidence of other causes of chronic liver disease.
Decompensated liver disease including ascites.
Evidence of alcohol abuse (> 20 gm/day) during the last 6 months.
Anticipated or current use or need for significant concomitant medical treatment including but not limited to systemic immunosuppressive drugs, cytotoxics, or chemotherapeutic agents.
History of recent acute hepatitis.
Clinical or radiological suspicion of Hepatocellular Carcinoma(HCC).
Presence of bleeding disorder.
Presence of cardiac pacemaker.
Contraindication to liver biopsy.

Study design
Purpose of the study
Diagnosis
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Not applicable
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/06/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
250
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 1684 0
3050
Recruitment postcode(s) [2] 1683 0
3065
Recruitment postcode(s) [3] 1682 0
3084
Recruitment postcode(s) [4] 1679 0
3181

Funding & Sponsors
Funding source category [1] 4920 0
Hospital
Name [1] 4920 0
Alfred Hospital
Country [1] 4920 0
Australia
Primary sponsor type
Hospital
Name
Alfred Hospital
Address
Gastroenterology unit 4th floor, Commercial road , Prahran, Vic 3181
Country
Australia
Secondary sponsor category [1] 4449 0
None
Name [1] 4449 0
Address [1] 4449 0
Country [1] 4449 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 6985 0
Alfred Health
Ethics committee address [1] 6985 0
Ethics department, Commercial road , Prahran, Vic, 3181
Ethics committee country [1] 6985 0
Australia
Date submitted for ethics approval [1] 6985 0
27/05/2009
Approval date [1] 6985 0
Ethics approval number [1] 6985 0
Ethics committee name [2] 6986 0
Saint Vincents Health
Ethics committee address [2] 6986 0
Ethics department, 41 Victoria Pde
Fitzroy, VIC 3065
Ethics committee country [2] 6986 0
Australia
Date submitted for ethics approval [2] 6986 0
27/05/2009
Approval date [2] 6986 0
Ethics approval number [2] 6986 0
Ethics committee name [3] 6993 0
Melbourne Health
Ethics committee address [3] 6993 0
Ethics dept.,Grattan Street, Parkville, VIC 3050
Ethics committee country [3] 6993 0
Australia
Date submitted for ethics approval [3] 6993 0
27/05/2009
Approval date [3] 6993 0
Ethics approval number [3] 6993 0
Ethics committee name [4] 6994 0
Southern Health
Ethics committee address [4] 6994 0
Ethics dept., 246 Clayton Road, Clayton.
Victoria 3168
Ethics committee country [4] 6994 0
Australia
Date submitted for ethics approval [4] 6994 0
27/05/2009
Approval date [4] 6994 0
Ethics approval number [4] 6994 0
Ethics committee name [5] 6995 0
Austin Health
Ethics committee address [5] 6995 0
Ethics dept.,
145 Studley Road
Heidelberg
Victoria
Australia, 3084
Ethics committee country [5] 6995 0
Australia
Date submitted for ethics approval [5] 6995 0
27/05/2009
Approval date [5] 6995 0
Ethics approval number [5] 6995 0

Summary
Brief summary
Chronic hepatitis B virus infection(HBV) affects 400 million people worldwide. It leads to 1.2 million deaths annually. An individual's prognosis when affected by the disease is related to it's severity.Patients who have cirrhosis as a result of HBV have high rates of complications such as liver cancer and gastrointestinal bleeding.Patients with advancing disease therefore have a more compelling need for treatment ,thus accurate evaluation is essential.
Liver biopsy up until now has been the gold standard for evaluation but it has many complications(incuding bleeding and death),contraindications and error .It is not suitable for serial assessment.
A new device that has been developed in this regard is fibroscan.Fibroscan measures liver stiffness which equates to liver fibrosis(disease). It does this by transmitting a wave impulse through the liver.The faster the wave travels the more fibrosed the liver is.It is a non-invasive and painless procedure much like an ultrasound.
Blood markers to assess liver fibrosis are also available but have not been well evaluated in patients with HBV.
We propose to recruit 250 participants with chronic HBV from several Melbourne hopitals who are undergoing liver biopsy as part of their routine care.Participants will be required to fill in a detailed questionnaire in order to evaluate further their liver disease .Within 4 weeks of the biopsy a fibroscan will be performed along with blood tests helping to assess the degree of liver fibrosis.
We willl compare the results of these non-invasive tests with liver biopsy results to review the diagnostic accuracy of fibroscan and blood fibrosis markers. We will also follow the participants for 2 years with annual fibroscans and blood tests to estimate progression of fibrosis and the affects of anti-viral medication on fibrosis.We also hope to assess the role of insensitivity to the body's natural insulin production to progression of liver fibrosis in patients with HBV by simply measuring fasting blood insulin and glucose levels and comparing these to the liver biopsy results.Insulin insensitivity has been confimed as an independent risk factor for liver fibrosis in a previous study of Hepatitis C patients,this has not yet been shown in a Hepatitis B population.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29544 0
Address 29544 0
Country 29544 0
Phone 29544 0
Fax 29544 0
Email 29544 0
Contact person for public queries
Name 12791 0
Dr Stephen Casey
Address 12791 0
Gastroenterology unit 4th floor, Alfred Hospital, Commercial road , Prahran, Vic 3181
Country 12791 0
Australia
Phone 12791 0
+61 3 9076 2223/+61 450 378 005
Fax 12791 0
Email 12791 0
s.casey@alfred.org.au
Contact person for scientific queries
Name 3719 0
Dr Stephen Casey
Address 3719 0
Gastroenterology unit 4th floor, Alfred Hospital, Commercial road , Prahran, Vic 3181
Country 3719 0
Australia
Phone 3719 0
+61 3 9076 2223/+61 450 378 005
Fax 3719 0
Email 3719 0
s.casey@alfred.org.au

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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