- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01491295
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
- 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)
- 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.
- 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.
- Theoretically, TDF can replace LAM/ADV when viral suppression has been achieved by LAM/ADV combination treatment in LAM-R CHB patients.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Yi-Hsiang Huang, MD, PhD
- Phone Number: 3055 886-2-28712121
- Email: yhhuang@vghtpe.gov.tw
Study Locations
-
-
-
Taipei, Taiwan, 11217
- Recruiting
- Taipei Veterans General Hospital-Division of Gastroenterology
-
Principal Investigator:
- Yi-Hsiang Huang
-
Contact:
- Yi-Hsiang Huang
- Phone Number: 3055 886-28712121
- Email: yhhuang@vghtpe.gov.tw
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- HBsAg-positive for more than 6 months (HBeAg-positive or HBeAg-negative).
- Age > 20 y/o.
- Under lamivudine/adefovir treatment for more than 1 year due to previous lamivudine resistance (LAM-R), current HBV DNA is undetectable (< 20 IU/ml) during enrollment.
Exclusion Criteria:
- HCV, HIV, HDV coinfection.
- Uncontrolled HCC, malignancy or decompensated liver cirrhosis (CTP score ≥ 7).
- Uremia patients or Creatinine ≥ 2 mg/dl.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Lamivudine plus adefovir
Continue lamivudine/adefovir add on treatment (standard treatment)
|
Lamivudine 100mg QD for 36 months (adjust dosage according to renal function) Adefovir 10mg QD for 36 months (adjust dosage according to renal function)
Other Names:
|
Experimental: Tenofovir
Switch from lamivudine/adefovir add on threatment to tenofovir monotherapy
|
Tenofovir disoproxil fumarate 300mg QD for 36 months (adjust dosage according to renal function)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Incidence of virological breakthrough (defined as HBV DNA > 100 IU/ml)
Time Frame: Sustained viral suppression after switching to TDF for 36 months
|
Sustained viral suppression after switching to TDF for 36 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
HBeAg seroconversion (for HBeAg-positive patients)
Time Frame: HBeAg seroconversion rate at 1, 2 and 3 years
|
HBeAg seroconversion rate at 1, 2 and 3 years
|
Incidence of HBsAg loss
Time Frame: Incidence of HBsAg loss at 1-, 2-, and 3 -years
|
Incidence of HBsAg loss at 1-, 2-, and 3 -years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Yi-Hsiang Huang, Taipei Veterans General Hospital, Taiwan
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Hepatitis, Chronic
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Tenofovir
- Lamivudine
- Adefovir
Other Study ID Numbers
- IN-US-174-0194
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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