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

NCT ID: NCT01491295

Last Updated: 2016-04-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2019-12-31

Brief 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.

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.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lamivudine plus adefovir

Continue lamivudine/adefovir add on treatment (standard treatment)

Group Type: ACTIVE_COMPARATOR

Lamivudine plus adefovir

Intervention Type: DRUG

Lamivudine 100mg QD for 36 months (adjust dosage according to renal function) Adefovir 10mg QD for 36 months (adjust dosage according to renal function)

Tenofovir

Switch from lamivudine/adefovir add on threatment to tenofovir monotherapy

Group Type: EXPERIMENTAL

Tenofovir disoproxil fumarate

Intervention Type: DRUG

Tenofovir disoproxil fumarate 300mg QD for 36 months (adjust dosage according to renal function)

Interventions

Tenofovir disoproxil fumarate

Tenofovir disoproxil fumarate 300mg QD for 36 months (adjust dosage according to renal function)

Intervention Type: DRUG

Lamivudine plus adefovir

Lamivudine 100mg QD for 36 months (adjust dosage according to renal function) Adefovir 10mg QD for 36 months (adjust dosage according to renal function)

Intervention Type: DRUG

Other Intervention Names

Viread; Zeffix; Hepsera

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kaohsiung Medical University Chung-Ho Memorial Hospital

OTHER

Sponsor Role: collaborator

China Medical University Hospital

OTHER

Sponsor Role: collaborator

Chi Mei Medical Hospital

OTHER

Sponsor Role: collaborator

Chiayi Christian Hospital

OTHER

Sponsor Role: collaborator

Taipei Veterans General Hospital, Taiwan

OTHER_GOV

Sponsor Role: lead

Responsible Party

vghtpe user

Professor: Yi-Hsiang Huang

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yi-Hsiang Huang

Role: PRINCIPAL_INVESTIGATOR

Taipei Veterans General Hospital, Taiwan

Locations

Taipei Veterans General Hospital-Division of Gastroenterology

Taipei, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Yi-Hsiang Huang, MD, PhD

Role: CONTACT

yhhuang@vghtpe.gov.tw

886-2-28712121 ext. 3055

Facility Contacts

Yi-Hsiang Huang

Role: primary

yhhuang@vghtpe.gov.tw

886-28712121 ext. 3055

Other Identifiers

IN-US-174-0194

Identifier Type: -

Identifier Source: org_study_id