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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2012 by Yonsei University.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Sang Hoon Ahn, Yonsei University
ClinicalTrials.gov Identifier:
NCT01595633
First received: March 11, 2012
Last updated: May 9, 2012
Last verified: May 2012
  Purpose

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).


Condition Intervention Phase
Chronic Hepatitis B
Drug: Switching from adefovir (10mg/day) to tenofovir (300mg/day)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Study Comparing Nucleoside Analogues Plus Tenofovir and Nucleoside Analogues Plus Adefovir in Chronic Hepatitis B Patients With Suboptimal Response to Adefovir-based Combination Therapy Due to Nucleoside Analogues Resistance

Resource links provided by NLM:


Further study details as provided by Yonsei University:

Primary Outcome Measures:
  • number of patients with complete virologic response (HBV DNA < 60 IU/mL, approximately 300 copies/mL) at 48 weeks treatment [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Complete virologic response (HBV DNA < 60 IU/mL, approximately 300 copies/mL) at 48 weeks treatment


Secondary Outcome Measures:
  • number of patients with antiviral response at 48 weeks therapy [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    number of patients with antiviral response (defined as decrement of HBV DNA level with 2 Log from baseline) at 48 weeks therapy

  • number of patients with biochemical response at 48 weeks therapy [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    number of patients with biochemical response (defined as ALT normalization) at 48 weeks therapy

  • number of patients with serologic response at 48 weeks therapy [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    number of patients with serologic response (defined as HBeAg seroconversion in case of HBeAg-positive hepatitis) at 48 weeks therapy

  • number of patients with appearance of resistant mutant strain at 48 weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    number of patients with appearance of resistant mutant strain at 48 weeks

  • Number of Participants with Adverse Events [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Number of Participants with Adverse Events during treatments (Adverse effects will be monitored every visit using physical examination and routine blood chemistry tests.)


Estimated Enrollment: 124
Study Start Date: March 2012
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Adefovir, nucleoside analogues
Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg) + Adefovir 10mg
Drug: 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
Other Name: Switching from adefovir (10mg/day) to tenofovir (300mg/day)
Experimental: Tenofovir, nucleoside analogues
Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg) + Tenofovir 300mg
Drug: 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
Other Name: Switching from adefovir (10mg/day) to tenofovir (300mg/day)

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).

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01595633

Contacts
Contact: BeomKyung Kim, Dr. 82-2-2228-1930 beomkkim@yuhs.ac

Locations
Korea, Republic of
Department of Internal Medicine, Yonsei University College of Medicine Recruiting
Seoul, Korea, Republic of, 120-752
Contact: BeomKyung Kim, Dr    +82-2-2228-1930    beomkkim@yuhs.ac   
Contact: Jun Yong Park, Dr    +82-2-2228-1994    DRPJY@yuhs.ac   
Sponsors and Collaborators
Yonsei University
Investigators
Principal Investigator: Sang Hoon Ahn, MD, PhD. Department of Internal Medicine, Yonsei University College of Medicine
  More Information

No publications provided

Responsible Party: Sang Hoon Ahn, Associate Professor, Yonsei University
ClinicalTrials.gov Identifier: NCT01595633     History of Changes
Other Study ID Numbers: 4-2011-0937
Study First Received: March 11, 2012
Last Updated: May 9, 2012
Health Authority: Korea: Institutional Review Board

Keywords provided by Yonsei University:
nucleoside analogue
adefovir
tenofovir
hepatitis B

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

ClinicalTrials.gov processed this record on August 01, 2014