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Switch to Tenofovir Versus Continue Lamivudine/Adefovir Treatment in Lamivudine-resistance Chronic Hepatitis B Patients

Information source: Taipei Veterans General Hospital, Taiwan
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Chronic Hepatitis B

Intervention: Tenofovir disoproxil fumarate (Drug); Lamivudine plus adefovir (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Taipei Veterans General Hospital, Taiwan

Official(s) and/or principal investigator(s):
Yi-Hsiang Huang, Principal Investigator, Affiliation: Taipei Veterans General Hospital, Taiwan

Overall contact:
Yi-Hsiang Huang, MD, PhD, Phone: 886-2-28712121, Ext: 3055, Email: yhhuang@vghtpe.gov.tw

Summary

1. Adefovir add-on therapy is superior to switching to adefovir monotherapy or entecavir 1mg monotherapy for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R) 2. Long-term adefovir add-on therapy was effective for viral suppression. However, the economic burden for such dual antiviral therapy is heavy because of infinite treatment. 3. Tenofovir disoproxil fumarate (TDF) is a potent antiviral agent. TDF demonstrated potent antiviral efficacy in a subset of lamivudine experienced HBeAg-positive patients. TDF is also superior to ADV in HBeAg-negative and HBeAg-positive treatment-naive patients. 4. Theoretically, TDF can replace LAM/ADV when viral suppression has been achieved by LAM/ADV combination treatment in LAM-R CHB patients.

Clinical Details

Official title: Randomized Trial of Switch to Tenofovir Versus Continue Lamivudine/Adefovir Treatment in Lamivudine-resistance Chronic Hepatitis B Patients Who Have Undergone Lamivudine/Adefovir Add-on Treatment

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Incidence of virological breakthrough (defined as HBV DNA > 100 IU/ml)

Secondary outcome:

HBeAg seroconversion (for HBeAg-positive patients)

Incidence of HBsAg loss

Detailed description: Hepatitis B virus (HBV) is a partially double-stranded DNA virus. HBV infection can induce a spectrum of disease ranging from asymptomatic infection to severe chronic liver diseases, including cirrhosis and hepatocellular carcinoma (HCC). Chronic HBV infection is also a major cause of HCC in Taiwan. Over 350 millions people worldwide are chronically infected with HBV. Lamivudine was the first marketing and is the first-line oral anti-viral agent for the therapy of chronic hepatitis B. Infinite nucleoside analogue therapy may be needed for long-term viral suppression especially in patients with HBeAg-negative chronic hepatitis B. The initial randomized studies demonstrated the clinical benefit and safety of lamivudine in

both hepatitis B e antigen (HBeAg)-positive and - negative chronic hepatitis B patients. But

as high as 20% of the cases under 1-year lamivudine treatment developed genotypic resistance, which defined as the presence of YMDD mutation on the HBV polymerase region. Genotypic resistance is almost always associated with virological breakthrough and exacerbation of liver function. Long-term lamivudine therapy was reported increase HBeAg seroconversion and provided clinical improvement in ALT levels. However, in a four-year follow-up study, YMDD-variant HBV was detected in as high as 67% of patients under lamivudine treatment. Several clinical studies have proven that adefovir add-on therapy is superior to switching to adefovir monotherapy or entecavir 1mg monotherapy for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R). Currently, AASLD and EASL guidelines recommend adefovir add-on therapy as a standard treatment for LAM-R CHB patients. Long-term adefovir add-on therapy was effective for viral suppression (8). However, the economic burden for such dual antiviral therapy is heavy because of infinite treatment. Tenofovir disoproxil fumarate (TDF) is a potent antiviral agent. TDF and ETV are recommended oral first-line therapies for CHB. TDF demonstrated potent antiviral efficacy in a subset of lamivudine experienced HBeAg-positive patients. TDF is also superior to ADV in HBeAg-negative and HBeAg-positive treatment-naive patients. Theoretically, TDF can replace LAM/ADV when viral suppression has been achieved by LAM/ADV combination treatment in LAM-R CHB patients. This clinical trial is a proof of concept study to evaluate the efficacy of switching to TDF monotherapy in such patients.

Eligibility

Minimum age: 20 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- HBsAg-positive for more than 6 months (HBeAg-positive or HBeAg-negative)

- Age > 18 y/o

- Under lamivudine/adefovir treatment for more than 1 year due to previous lamivudine

resistance (LAM-R), current HBV DNA is undetectable by Cobas TagMan Assay (<12 IU/ml) during enrollment. Exclusion Criteria:

- HCV, HIV, HDV coinfection

- Co-existing HCC, malignancy or decompensated liver cirrhosis (CTP score >=7)

- Uremia patients

Locations and Contacts

Yi-Hsiang Huang, MD, PhD, Phone: 886-2-28712121, Ext: 3055, Email: yhhuang@vghtpe.gov.tw

Taipei Veterans General Hospital-Division of Gastroenterology, Taipei 11217, Taiwan; Recruiting
Yi-Hsiang Huang, Phone: 886-28712121, Ext: 3055, Email: yhhuang@vghtpe.gov.tw
Yi-Hsiang Huang, Principal Investigator
Additional Information

Starting date: September 2012
Last updated: November 2, 2012

Page last updated: August 23, 2015

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