TDF VS LAM + ADV in LAM + ADV Treated LAM-resistant CHB Patients With Undetectable Hepatitis B Virus DNA
Chronic Hepatitis B
Drug: Lamivudine plus adefovir
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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.|
- 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.
- 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
|Study Start Date:||November 2012|
|Estimated Study Completion Date:||April 2016|
|Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Lamivudine plus adefovir
Continue lamivudine/adefovir add on treatment (standard treatment)
Drug: Lamivudine plus adefovir
Lamivudine 100mg QD for 96 weeks + Adefovir 10mg QD for 96 weeks
Switch from lamivudine/adefovir add on treatment to tenofovir monotherapy
Tenofovir 300mg QD for 96 weeks
Other Name: Viread
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01732367
|Korea, Republic of|
|Department of Internal Medicine, Keimyung University Dongsan Medical Center|
|Daegu, Korea, Republic of, ASI|KR|KS002|TAEGU|
|Principal Investigator:||Byoung Kuk Jang, M.D||Department of Internal Medicine, Keimyung University Dongsan Medical Center|