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Trial registered on ANZCTR


Registration number
ACTRN12619001441101p
Ethics application status
Not yet submitted
Date submitted
17/09/2019
Date registered
17/10/2019
Date last updated
17/10/2019
Date data sharing statement initially provided
17/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Can we stop antiviral medicines safely and effectively in patients with chronic hepatitis B and help to increase the chance of cure?
Scientific title
Discontinuing nucleos(t)ide analogue therapy for chronic hepatitis B -Is it safe and will it increase the rate of HBsAg seroconversion? A randomised pilot study
Secondary ID [1] 299304 0
nil known
Universal Trial Number (UTN)
U1111-1239-5650
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B 314433 0
Condition category
Condition code
Infection 312776 312776 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group 1: patients will stop antiviral treatment and have close observation (monthly blood tests for the first 12 months, then 3 monthly thereafter for up to 5 years)
Group 2: standard of care patients to continue antiviral treatment as usual (3 monthly blood tests)

Strategies used to monitor adherence to intervention- direct questioning by study personnel at each clinic visit
We would do interim analysis at 12 months and based on the results at this point determine whether we would continue or terminate the study.
Intervention code [1] 315589 0
Treatment: Other
Comparator / control treatment
Randomized controlled study - the control group will be group 2 which will remain on antiviral treatment as per standard of care.
Control group
Active

Outcomes
Primary outcome [1] 321415 0
1) Rates of HBsAg loss (this is a blood test and patients would either have lost HBsAg or not lost HBsAg
Timepoint [1] 321415 0
Outcome 1: rates of HBsAg loss at end of year 1 and year 5
Primary outcome [2] 321416 0
2) Rates of sustained virological response off treatment (defined by serum HBV DNA <2000IU/mL plus serum ALT (alanine aminotransferase) level <ULN (upper limit of normal) between week 24 and week 52 (end of first study year) and up to 5 years
Timepoint [2] 321416 0
week 24, week 52 and year 5
Secondary outcome [1] 374910 0
1) rates of Virological relapse (increase in HBV DNA level >2000 IU/mL or increase by >=1 log10 from nadir in 2 consecutive measurements at least 3 months apart)
This is done via a blood test for HBV DNA and comparing it to the baseline level
Timepoint [1] 374910 0
within year 1 and rates of virological relapse up to 5 years
HBV DNA will be checked once monthly in the intervention arm for the first 6 months, thereafter 3 monthly.
In the control arm, HBV DNA is checked every 3 months
Secondary outcome [2] 374911 0
2) rates of biochemical relapse (increase in ALT level >2x ULN)
This is a blood test- we would calculate the percentage of patients in each group who have achieved this outcome of elevated ALT to twice the upper limit of normal during any time in the study period
Timepoint [2] 374911 0
by year 1 and year 5
Secondary outcome [3] 374912 0
3) rates of hepatitis flare (increase in ALT> 10x ULN)

this is a blood test.
Timepoint [3] 374912 0
year 1 and year 5
Secondary outcome [4] 374913 0
4) changes in quantitative HBsAg levels

this is a blood test of the HBsAg levels-
Timepoint [4] 374913 0
year 1 and year 5
HBsAg levels will be done every month for the first 6 months then 3 monthly. In the control arm it is done every 3 months (we don't expect much change in the HBsAg levels in the control arm based on results from previous studies)

Eligibility
Key inclusion criteria
- Non-cirrhotic patients with chronic hepatitis B (CHB), on nucleos(t)ide analogue (NA) therapy for at least 2 years
- Age 18-60 years
- Normal ALT level at screening
- HBV DNA undetectable levels x3 (>6 months apart)
- HBsAg levels <100 IU/mL within the last 3 months
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with cirrhosis/severe fibrosis (Fibroscan >9kpa), hepatocellular carcinoma
- Other significant medical co-morbidities
- Patients who have history of significant non compliance
- Significant alcohol consumption (>30g/day for women and >50g/day for men)
- Poor venous access

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
allocation concealed and done by sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
each eligible patient will be randomized on day 1 by randomly selecting a sealed opaque envelope from the pile that has been all mixed up in a container.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
previous studies have shown up to 79.2% HBsAg seroclearance rates by year 6 for patients with HBsAg levels <120Iu/mL at baseline.
by selecting patients with only HBsAg levels <100Iu/mL at baseline we expect to see at least similar rates. compared to historical data for standard of care patients with only <5% achieving HBsAg seroclearance we estimate that having 20 patients per arm should have the power to demonstrate a difference with 99% confidence

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
5/11/2019
Actual
Date of last participant enrolment
Anticipated
16/06/2020
Actual
Date of last data collection
Anticipated
16/06/2025
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment outside Australia
Country [1] 21867 0
New Zealand
State/province [1] 21867 0
auckland

Funding & Sponsors
Funding source category [1] 303826 0
Hospital
Name [1] 303826 0
Middlemore Hospital
Country [1] 303826 0
New Zealand
Primary sponsor type
Individual
Name
Dr Tien Huey Lim
Address
Department of Gastroenterology
Middlemore Hospital
100 Hospital Road, Papatoetoe, Auckland 2025
Country
New Zealand
Secondary sponsor category [1] 303952 0
None
Name [1] 303952 0
Address [1] 303952 0
Country [1] 303952 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 304340 0
Northern A health and disability ethics committee
Ethics committee address [1] 304340 0
Ethics Committee
Health Research Council
P O Box 5541
Wellesley Street
Auckland 1141
ethics@hrc.govt.nz
Ethics committee country [1] 304340 0
New Zealand
Date submitted for ethics approval [1] 304340 0
01/11/2019
Approval date [1] 304340 0
Ethics approval number [1] 304340 0

Summary
Brief summary
The current internationally accepted endpoint for chronic hepatitis B (CHB) treatment is loss of hepatitis B surface antigen (HBsAg), but this is rarely achieved. Recent studies have shown that stopping antiviral treatment in a highly selected group of patients ie non cirrhotic patients who have had undetectable HBV DNA on treatment for at least 1-2 years with low baseline HBsAg level can increase the chance of HBsAg loss ie functional cure, and a large proportion (50%) also had sustained virological response off treatment and not required retreatment. We aim to perform a randomized pilot study of 40 non cirrhotic patients at Middlemore Hospital with low baseline HBsAg <100IU/mL to determine whether it is safe to stop antiviral treatment and whether this will help improve the chance of functional cure from hepatitis B.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96606 0
Dr Tien Huey Lim
Address 96606 0
Department of Gastroenterology
Middlemore Hospital
100 Hospital Road, Papatoetoe, Auckland 2025
Country 96606 0
New Zealand
Phone 96606 0
+64 212303453
Fax 96606 0
Email 96606 0
tienhuey.lim@middlemore.co.nz
Contact person for public queries
Name 96607 0
Tien Huey Lim
Address 96607 0
Department of Gastroenterology
Middlemore Hospital
100 Hospital Road, Papatoetoe, Auckland 2025
Country 96607 0
New Zealand
Phone 96607 0
+64 212303453
Fax 96607 0
Email 96607 0
tienhuey.lim@middlemore.co.nz
Contact person for scientific queries
Name 96608 0
Tien Huey Lim
Address 96608 0
Department of Gastroenterology
Middlemore Hospital
100 Hospital Road, Papatoetoe, Auckland 2025
Country 96608 0
New Zealand
Phone 96608 0
+64 212303453
Fax 96608 0
Email 96608 0
tienhuey.lim@middlemore.co.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
no individual data will be shared but results will be published as a group vs group comparison


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.