Switch From Adefovir to Tenofovir in Chronic Hepatitis B for Suboptimal Response to Adefovir-based Combination Therapy

NCT ID: NCT01595633

Last Updated: 2012-05-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2014-02-28

Brief Summary

In Korea, the number of suboptimal responders to rescue combination therapy is also increasing. As a matter of fact, according to the investigations in Korea, HBV DNA undetectability at 48 weeks of adefovir and lamivudine combination rescue therapy for patients with lamivudine resistance was reported to be only 32.4%, which suggested that the appropriate another rescue therapy might be urgently required. However, there is no promising oral antiviral agents to control these patients in Asia-Pacific region, where tenofovir is not widely available. Tenofovir has a higher potent antiviral efficacy and a negligible drug resistance rate. The switch from adefovir to tenofovir in patients who have insufficient hepatitis B virus (HBV) suppression (HBV DNA ≥ 60 IU/mL by PCR) may lead to increased viral suppression or more HBeAg loss/seroconversion.

Here, the investigators aimed to conduct a randomized study on evaluating the antiviral efficacy, safety, and tolerability of switching from adefovir to tenofovir in chronic hepatitis B patients who have suboptimal response to adefovir-based combination rescue therapy due to nucleoside analogues Resistance (SATIS study).

Detailed Description

The major goal of antiviral therapy against chronic hepatitis B is to suppress viral replications successfully, ultimately preventing the chronic liver damage, development of liver cirrhosis and hepatocellular carcinoma. In Korea, the number of multi-drug resistant CHB has been rapidly increased last few years. It is because that the national health insurance coverage is very limited for the patients who experienced primary treatment failure. The only switch to adefovir has been allowed in lamivudine resistant patients and thus this sequential rescue therapy generated multi-drug resistance to both adefovir and another drugs. Thus, nowadays, add-on therapy rather than switch therapy might be preferred from major guidelines in this point.

However, the number of suboptimal responders to rescue combination therapy is also increasing. As a matter of fact, according to the investigations in Korea, HBV DNA undetectability at 48 weeks of adefovir and lamivudine combination rescue therapy for patients with lamivudine resistance was reported to be only 32.4%, which suggested that the appropriate another rescue therapy might be urgently required. However, there is no promising oral antiviral agents to control these patients in Asia-Pacific region, where tenofovir is not widely available. Tenofovir has a higher potent antiviral efficacy and a negligible drug resistance rate. It belongs to the different class compared to other oral nucleoside analogues (NAs) such as lamivudine, telbivudine, clevudine and entecavir. The switch from adefovir to tenofovir in patients who have insufficient hepatitis B virus (HBV) suppression (HBV DNA ≥ 60 IU/mL by PCR) may lead to increased viral suppression or more HBeAg loss/seroconversion. The results of this study will provide a rationale for switch from adefovir to tenofovir in combination to another drug continued (lamivudine, telbivudine, clevudine and entecavir).

Here, the investigators aimed to conduct a randomized study on evaluating the antiviral efficacy, safety, and tolerability of switching from adefovir to tenofovir in chronic hepatitis B patients who have suboptimal response to adefovir-based combination rescue therapy due to nucleoside analogues Resistance (SATIS study).

Conditions

Chronic Hepatitis B

Study Design

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

Study Groups

Adefovir, nucleoside analogues

Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg) + Adefovir 10mg

Group Type: ACTIVE_COMPARATOR

Switching from adefovir (10mg/day) to tenofovir (300mg/day)

Intervention Type: DRUG

active comparator: Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg/day) + Adefovir 10mg/day Experimental: Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg/day) + Tenofovir 300mg/day

Tenofovir, nucleoside analogues

Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg) + Tenofovir 300mg

Group Type: EXPERIMENTAL

Switching from adefovir (10mg/day) to tenofovir (300mg/day)

Intervention Type: DRUG

active comparator: Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg/day) + Adefovir 10mg/day Experimental: Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg/day) + Tenofovir 300mg/day

Interventions

Switching from adefovir (10mg/day) to tenofovir (300mg/day)

active comparator: Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg/day) + Adefovir 10mg/day Experimental: Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg/day) + Tenofovir 300mg/day

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• subjects with age >= 20 years
• subjects with chronic hepatitis B
• subjects treated with nucleoside analogues plus adefovir for at least 6 months due to resistance to nucleoside analogues (Lamivudine, Telbivudine, Entecavir, or Clevudine)
• subjects with partial virologic response to nucleoside analogues plus adefovir HBV DNA ≥ 60 IU/mL)
• subjects with ALT less than 5 times of upper limit of normal
• subjects who agreed to participate in the clinical trials and signed the informed consents

Exclusion Criteria

• subjects with decompensate liver cirrhosis Child-Pugh B, C)
• subjects with Adefovir mutation
• subjects with HCV, HDV, or HIV infection
• pregnant or lactating women
• women of childbearing age who do not use the appropriate contraception method
• subjects who have the abnormal lesion suspected of hepatocellular carcinoma on imaging modalities
• subjects with other liver diseases such as hemochromatosis, Wilson's disease, alcoholic liver disease, nonalcoholic liver disease, alpha-1 antitrypsin deficiency
• subjects with hypersensitivity for study drugs
• subjects who participated in other clinical trials 60 days before the current recruitment
• subjects who are judged as inappropriate by investigators

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

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Sang Hoon Ahn

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sang Hoon Ahn, MD, PhD.

Role: PRINCIPAL_INVESTIGATOR

Department of Internal Medicine, Yonsei University College of Medicine

Locations

Department of Internal Medicine, Yonsei University College of Medicine

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

BeomKyung Kim, Dr.

Role: CONTACT

beomkkim@yuhs.ac

82-2-2228-1930

Facility Contacts

BeomKyung Kim, Dr

Role: primary

beomkkim@yuhs.ac

+82-2-2228-1930

Jun Yong Park, Dr

Role: backup

DRPJY@yuhs.ac

+82-2-2228-1994

Other Identifiers

4-2011-0937

Identifier Type: -

Identifier Source: org_study_id