TDF VS LAM + ADV in LAM + ADV Treated LAM-resistant CHB Patients With Undetectable Hepatitis B Virus DNA

This study is enrolling participants by invitation only.
Sponsor:
Collaborators:
Kyungpook National University
Daegu Catholic University Medical Center
DongGuk University
Pusan National University Hospital
Yeungnam University
Information provided by (Responsible Party):
Jang Byoung Kuk, Keimyung University Dongsan Medical Center
ClinicalTrials.gov Identifier:
NCT01732367
First received: November 19, 2012
Last updated: February 23, 2014
Last verified: February 2014

November 19, 2012
February 23, 2014
November 2012
February 2016   (final data collection date for primary outcome measure)
Percentage number of patients with virus reactivation [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
Percentage number of patients with virus reactivation (HBV DNA > 40 IU/mL on two consecutive samples taken 1 month apart, or persistent HBV DNA levels of 20-40 IU/mL on three consecutive 1 month interval) at Week 96 while on treatment.
Same as current
Complete list of historical versions of study NCT01732367 on ClinicalTrials.gov Archive Site
  • Virologic response [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
    Virologic response Percentage number of patients with virus reactivation at Week 48
  • Antiviral resistance [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
    Antiviral resistance percentage number of patients who developed drug resistant mutation at Week 48 and 96 while on randomized therapy.
  • Biochemical response [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
    Biochemical response percentage number of patients with biochemical breakthrough at Week 48 and 96
  • Serologic response [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
    Serologic response (1) HBeAg loss/seroconversion in HBeAg-positive CHB Percentage number of patients with HBeAg loss or seroconversion at Week 48 and 96.
  • Serologic response [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
    Serologic response (2) HBsAg loss Percentage number of patients with HBsAg loss at Week
  • Safety assessment [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
    Safety assessment
1. Virologic response 2. Antiviral resistance 3. Biochemical response 4. Serologic response 5. Safety assessment [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
  1. Virologic response Percentage number of patients with virus reactivation at Week 48.
  2. Antiviral resistance percentage number of patients who developed drug resistant mutation at Week 48 and 96 while on randomized therapy.
  3. Biochemical response percentage number of patients with biochemical breakthrough at Week 48 and 96.
  4. Serologic response (1) HBeAg loss/seroconversion in HBeAg-positive CHB Percentage number of patients with HBeAg loss or seroconversion at Week 48 and 96.

(2) HBsAg loss Percentage number of patients with HBsAg loss at Week 96. 5. Safety assessment

Not Provided
Not Provided
 
TDF VS LAM + ADV in LAM + ADV Treated LAM-resistant CHB Patients With Undetectable Hepatitis B Virus DNA
Randomized Trial of Tenofovir Versus Lamivudine Plus Adefovir in Lamivudine Plus Adefovir Treated Lamivudine-resistant Chronic Hepatitis B Patients With Undetectable Hepatitis B Virus DNA.

This study will provide a rationale for switch from lamivudine plus adefovir to tenofovir monotherapy in Lamivudine plus Adefovir Treated Lamivudine-resistant chronic hepatitis B patients with Undetectable Hepatitis B Virus DNA

Recently, in Korea, long-term medication of antiviral agents and their resulting resistance expression have been the most serious cause of failure to treat chronic hepatitis B. Exp.

In particular, the annual resistance rate to lamivudine currently widely being used in Korea amounts to about 15 to 20 percents and the rate is expected to reach 70 to 80 percent in four to five years.

The guidelines by the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of the Liver (EASL) recommend a combination therapy with adefovir or tenofovir for patients with lamivudine resistant HBV .

In Korea, however, in case of combined prescription of lamivudine and adefovir, only one of them is covered by the health insurance and therefore many patients are difficult to continue treatment due to their economic conditions.

Tenofovir that has been developed most recently and will be placed on sale sooner or later in Korea has strong antiviral effects, causes little or no emergence of resistant viruses, and is known to have lower nephrotoxicity than adefovir.

In particular, several papers reported that tenofovir has effective and sustaining antiviral effects in patients who had other antiviral agents resistant HBV as well as those who received initial treatment. This shows that patients only with lamivudine resistant HBV can be treated only with tenofovir without a combination therapy and when they have low levels of HBV DNA, treatment is relatively effective despite their resistance to adefovir.

Therefore, it is considered that tenofovir switching therapy in patients with undetectable HBV DNA after lamivudine plus adefovir combination therapy to maintain their virus response.

The results of this study will provide a rationale for switch from lamivudine plus adefovir to tenofovir monotherapy in such patients.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Hepatitis B
  • Drug: Lamivudine plus adefovir
    Lamivudine 100mg QD for 96 weeks + Adefovir 10mg QD for 96 weeks
    Other Names:
    • Zeffix
    • Hepsera
  • Drug: Tenofovir
    Tenofovir 300mg QD for 96 weeks
    Other Name: Viread
  • Active Comparator: Lamivudine plus adefovir
    Continue lamivudine/adefovir add on treatment (standard treatment)
    Intervention: Drug: Lamivudine plus adefovir
  • Experimental: Tenofovir
    Switch from lamivudine/adefovir add on treatment to tenofovir monotherapy
    Intervention: Drug: Tenofovir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Enrolling by invitation
171
February 2016
February 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male and female patients aged 18 or older
  • The CHB patients (both HBeAg-positive and - negative) who have at least 6 months undetectable HBV DNA (serum HBV DNA ≤ 20 IU/mL) after lamivudine plus adefovir combination therapy.

Exclusion Criteria:

  • Patients with decompensated liver disease
  • Patients with HCV, HDV or HIV
  • Patients with HCC
  • Serum ALT > 2x ULN level
  • Serum creatinine > 2.0mg/dL
  • Pregnant or lactating women
  • Women who have a plan for pregnancy within the three coming years
  • Patients who have uncontrolled severe concomitant diseases— severe cardiovascular diseases and other infection
  • Those who have no capabilities to understand and sign an informed consent
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Korea, Republic of
 
NCT01732367
TDF0001
Yes
Jang Byoung Kuk, Keimyung University Dongsan Medical Center
Keimyung University Dongsan Medical Center
  • Kyungpook National University
  • Daegu Catholic University Medical Center
  • DongGuk University
  • Pusan National University Hospital
  • Yeungnam University
Principal Investigator: Byoung Kuk Jang, M.D Department of Internal Medicine, Keimyung University Dongsan Medical Center
Keimyung University Dongsan Medical Center
February 2014

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