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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
  Purpose
  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.

Condition Intervention Phase
Chronic Hepatitis B
Drug: Tenofovir disoproxil fumarate
Drug: Lamivudine plus adefovir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Taipei Veterans General Hospital, Taiwan:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 160
Study Start Date: September 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lamivudine plus adefovir
Continue lamivudine/adefovir add on treatment (standard treatment)
Drug: Lamivudine plus adefovir
Lamivudine 100mg QD for 36 months Adefovir 10mg QD for 36 months
Other Names:
  • Zeffix
  • Hepsera
Experimental: Tenofovir
Switch from lamivudine/adefovir add on threatment to tenofovir monotherapy
Drug: Tenofovir disoproxil fumarate
Tenofovir disoproxil fumarate 300mg QD for 36 months
Other Name: Viread

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

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01491295

Contacts
Contact: Yi-Hsiang Huang, MD, PhD 886-2-28712121 ext 3055 yhhuang@vghtpe.gov.tw

Locations
Taiwan
Taipei Veterans General Hospital-Division of Gastroenterology Recruiting
Taipei, Taiwan, 11217
Contact: Yi-Hsiang Huang    886-28712121 ext 3055    yhhuang@vghtpe.gov.tw   
Principal Investigator: Yi-Hsiang Huang         
Sponsors and Collaborators
Taipei Veterans General Hospital, Taiwan
Investigators
Principal Investigator: Yi-Hsiang Huang Taipei Veterans General Hospital, Taiwan
  More Information

No publications provided

Responsible Party: vghtpe user, Professor: Yi-Hsiang Huang, Taipei Veterans General Hospital,Taiwan
ClinicalTrials.gov Identifier: NCT01491295     History of Changes
Other Study ID Numbers: IN-US-174-0194
Study First Received: October 27, 2011
Last Updated: November 2, 2012
Health Authority: Taiwan : Food and Drug Administration

Keywords provided by Taipei Veterans General Hospital, Taiwan:
Lamivudine
adefovir add on treatment
tenofovir
chronic hepatitis B

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
DNA Virus Infections
Digestive System Diseases
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Adefovir
Adefovir dipivoxil
Lamivudine
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014