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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2011 by Taipei Veterans General Hospital, Taiwan
Sponsor:
Information provided by (Responsible Party):
vghtpe user, Taipei Veterans General Hospital,Taiwan
ClinicalTrials.gov Identifier:
NCT01491295
First received: October 27, 2011
Last updated: November 2, 2012
Last verified: December 2011

October 27, 2011
November 2, 2012
September 2012
December 2016   (final data collection date for primary outcome measure)
Incidence of virological breakthrough (defined as HBV DNA > 100 IU/ml) [ Time Frame: Sustained viral suppression after switching to TDF for 36 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01491295 on ClinicalTrials.gov Archive Site
  • HBeAg seroconversion (for HBeAg-positive patients) [ Time Frame: HBeAg seroconversion rate at 1, 2 and 3 years ] [ Designated as safety issue: No ]
  • Incidence of HBsAg loss [ Time Frame: Incidence of HBsAg loss at 1-, 2-, and 3 -years ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Switch to Tenofovir Versus Continue Lamivudine/Adefovir Treatment in Lamivudine-resistance Chronic Hepatitis B Patients
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
  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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Hepatitis B
  • Drug: Tenofovir disoproxil fumarate
    Tenofovir disoproxil fumarate 300mg QD for 36 months
    Other Name: Viread
  • Drug: Lamivudine plus adefovir
    Lamivudine 100mg QD for 36 months Adefovir 10mg QD for 36 months
    Other Names:
    • Zeffix
    • Hepsera
  • Active Comparator: Lamivudine plus adefovir
    Continue lamivudine/adefovir add on treatment (standard treatment)
    Intervention: Drug: Lamivudine plus adefovir
  • Experimental: Tenofovir
    Switch from lamivudine/adefovir add on threatment to tenofovir monotherapy
    Intervention: Drug: Tenofovir disoproxil fumarate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
160
December 2016
December 2016   (final data collection date for primary outcome measure)

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
Both
20 Years and older
No
Contact: Yi-Hsiang Huang, MD, PhD 886-2-28712121 ext 3055 yhhuang@vghtpe.gov.tw
Taiwan
 
NCT01491295
IN-US-174-0194
No
vghtpe user, Taipei Veterans General Hospital,Taiwan
Taipei Veterans General Hospital, Taiwan
Not Provided
Principal Investigator: Yi-Hsiang Huang Taipei Veterans General Hospital, Taiwan
Taipei Veterans General Hospital, Taiwan
December 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP