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
|