Finite Versus Continuous Nucleos(t)Ide Analogues for Chronic Hepatitis B

• Status: Active, not recruiting
• Trial end date: 2026-12-01
• Target enrollment: 0
• Participant gender: All

Summary

BACKGROUND:

Finite nucleos(t)ide 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 (age≥20 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 1:1 ratio to continue viral suppression with entecavir (0.5mg 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).

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: E-DA Hospital
• Treatments: Entecavir; Tenofovir

Criteria

Inclusion Criteria:

1. Age ≥ 20 years

2. Chronic hepatitis B virus infection (defined as positive HBsAg for ≥ 6 months)

3. Entecavir or tenofovir (either tenofovir disoproxil fumarate or tenofovir alafenamide) for at least two years and still on therapy at screening for this trial.

4. Fulfillment of the stopping rules recommended by the Asian-Pacific guidelines 2016:

• For patients with positive HBeAg prior to their antiviral treatment, HBeAg seroconversion needs to be documented and followed by consolidation treatment for at least one year). Besides, serum ALT is within normal limits and HBV DNA is undetectable.

• For those with negative HBeAg prior to the antiviral therapy, undetectable HBV DNA documented on three separate occasions (at least 6 months apart)

5. At screening for this study, HBsAg serology is positive, HBeAg negative, and HBV DNA undetectable in serum.

Exclusion Criteria:

1. Liver cirrhosis (either clinical or pathological diagnosis) at screening

2. Serious underlying disease (with valid certification of catastrophic illness) at screening

3. Manifestations and concerns of hepatic decompensation, including serum bilirubin >2mg/dL and/or prolongation of prothrombin time > 3 seconds at screening

4. Hepatitis C virus (if anti-HCV serology is positive, confirmation with detectable HCV RNA is required), human immunodeficiency virus (HIV) or hepatitis delta virus (HDV) coinfection at screening.

5. Prior history of any malignancy including liver cancer

6. Prior history of any organ transplantation

7. Prior history of drug resistance to any Nuc agent

8. Any patient condition that the treating physician deems inappropriate for enrollment in this trial