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

March 11, 2012
May 9, 2012
March 2012
February 2014   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01595633 on ClinicalTrials.gov Archive Site
  • 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.)
Same as current
Not Provided
Not Provided
 
Switch From Adefovir to Tenofovir in Chronic Hepatitis B for Suboptimal Response to Adefovir-based Combination Therapy
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

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).

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).

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Hepatitis B
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)
  • Active Comparator: Adefovir, nucleoside analogues
    Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg) + Adefovir 10mg
    Intervention: Drug: 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
    Intervention: Drug: Switching from adefovir (10mg/day) to tenofovir (300mg/day)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
124
February 2014
February 2014   (final data collection date for primary outcome measure)

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
Both
20 Years and older
No
Contact: BeomKyung Kim, Dr. 82-2-2228-1930 beomkkim@yuhs.ac
Korea, Republic of
 
NCT01595633
4-2011-0937
Yes
Sang Hoon Ahn, Yonsei University
Yonsei University
Not Provided
Principal Investigator: Sang Hoon Ahn, MD, PhD. Department of Internal Medicine, Yonsei University College of Medicine
Yonsei University
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP