Ignite Creation Date:
2024-05-06 @ 6:48 PM
Last Modification Date:
2024-10-26 @ 2:55 PM
Study NCT ID:
NCT05793268
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-03-31
First Post:
2022-12-19
Brief Title:
Finite Versus Continuous NucleostIde Analogues for Chronic Hepatitis B
Sponsor:
E-DA Hospital
Organization:
E-DA Hospital
Study Overview
Official Title:
Safety and Efficacy of Finite Versus Continuous NucleostIde Analogues Therapy in Patients With Chronic Hepatitis B A Multicenter Randomized Controlled Trial
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
BACKGROUND
Finite nucleostide analogue Nuc therapy was proposed as an alternative strategy in the management of chronic hepatitis B CHB but there remained not data from randomized controlled trials to clarify safety and efficacy of this treatment strategy
AIMS
The investigators aimed to evaluate the safety and efficacy of finite Nuc therapy versus continuous treatment in CHB patients without liver cirrhosis and also to identify factors that may predict therapeutic responses and clinical outcomes after withdrawal of Nuc treatment for CHB
MATERIAL AND METHODS
This is a multicenter randomized controlled trial conducted in Taiwan Eligible patients are adults age20 years with CHB chronic infection 6 months who fulfill the APASL guideline 2016 to stop NA therapy Those with cirrhosis malignancy organ transplant autoimmune disorder or serious underlying diseases including renal impairment were excluded A total of 360 patients will be enrolled Enrolled patients are randomly allocated with a 11 ratio to continue viral suppression with entecavir 05mg once daily or tenofovir disoproxil fumarate 300mg once daily or stop the treatment All patients will be followed up according to the protocol recommended by a panel of APASL experts The primary analysis for study outcomes is scheduled at 3 years after randomization and the primary outcome is seroclearance of HBsAg There will be interim analyses scheduled at one- and two-years following randomization of the first 200 patients and also one-and two years following randomization of the planned 360 patients to determine whether early termination of the trial may be justified by attainment of the efficacy endpoint 10 vs 1 of HBsAg seroclearance or concerns of the safety outcomes significant between-group difference in mortality acute on chronic liver failure or acute flares with hepatic decompensation
Finite nucleostide analogue Nuc therapy was proposed as an alternative strategy in the management of chronic hepatitis B CHB but there remained not data from randomized controlled trials to clarify safety and efficacy of this treatment strategy
AIMS
The investigators aimed to evaluate the safety and efficacy of finite Nuc therapy versus continuous treatment in CHB patients without liver cirrhosis and also to identify factors that may predict therapeutic responses and clinical outcomes after withdrawal of Nuc treatment for CHB
MATERIAL AND METHODS
This is a multicenter randomized controlled trial conducted in Taiwan Eligible patients are adults age20 years with CHB chronic infection 6 months who fulfill the APASL guideline 2016 to stop NA therapy Those with cirrhosis malignancy organ transplant autoimmune disorder or serious underlying diseases including renal impairment were excluded A total of 360 patients will be enrolled Enrolled patients are randomly allocated with a 11 ratio to continue viral suppression with entecavir 05mg once daily or tenofovir disoproxil fumarate 300mg once daily or stop the treatment All patients will be followed up according to the protocol recommended by a panel of APASL experts The primary analysis for study outcomes is scheduled at 3 years after randomization and the primary outcome is seroclearance of HBsAg There will be interim analyses scheduled at one- and two-years following randomization of the first 200 patients and also one-and two years following randomization of the planned 360 patients to determine whether early termination of the trial may be justified by attainment of the efficacy endpoint 10 vs 1 of HBsAg seroclearance or concerns of the safety outcomes significant between-group difference in mortality acute on chronic liver failure or acute flares with hepatic decompensation
Detailed Description:
Chronic hepatitis B virus HBV infection imposes a serious threat to global public health affecting more than 250 million individuals around the world In the management of patients with chronic hepatitis B CHB treatment with nucleostide analog Nuc has been shown to improve clinical outcomes including occurrence and recurrence of hepatocellular carcinoma HCC liver-related mortality and overall mortality Nuc therapy however cannot exterminate HBV and so continuous treatment is usually required to sustain viral inhibition Seroclearance of hepatitis B surface antigen HBsAg predicts durable remission off Nuc and may serve as the treatment endpoint but it rarely occurs with current regimen Therefore long-term to indefinite treatment is currently recommended
In view of various concerns such as drug exposure adherence and expense for a treatment course that could be lifelong a finite strategy of Nuc therapy was proposed to allow treatment withdrawal prior to HBsAg seroclearance Another major reason for the finite strategy is a higher chance of HBsAg seroclearance following treatment cessation Nevertheless viral replication almost always reactivates and often leads to clinical flares While an episode of acute flare might be self-limited or even conducive to HBsAg seroclearance it could progress to acute on chronic liver failure with fatal consequences Risks of these serious outcomes following treatment withdrawal need to be accurately quantified in order to inform the practice of finite Nuc therapy
Existent literature on the efficacy and safety of finite Nuc therapy remained very limited as recently shown in a systematic review and meta-analysis by Hall and colleagues In order to close the gaps in current knowledge the investigators conduct this multicenter randomized controlled trial to examine if cessation of Nuc is safe and conducive to HBsAg seroclearance
In view of various concerns such as drug exposure adherence and expense for a treatment course that could be lifelong a finite strategy of Nuc therapy was proposed to allow treatment withdrawal prior to HBsAg seroclearance Another major reason for the finite strategy is a higher chance of HBsAg seroclearance following treatment cessation Nevertheless viral replication almost always reactivates and often leads to clinical flares While an episode of acute flare might be self-limited or even conducive to HBsAg seroclearance it could progress to acute on chronic liver failure with fatal consequences Risks of these serious outcomes following treatment withdrawal need to be accurately quantified in order to inform the practice of finite Nuc therapy
Existent literature on the efficacy and safety of finite Nuc therapy remained very limited as recently shown in a systematic review and meta-analysis by Hall and colleagues In order to close the gaps in current knowledge the investigators conduct this multicenter randomized controlled trial to examine if cessation of Nuc is safe and conducive to HBsAg seroclearance
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None