Clinical trial NCT01732367: TDF VS LAM + ADV in LAM + ADV Treated LAM-resistant CHB Patients With Undetectable Hepatitis B Virus DNA
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hepatitis B
Keywords: Tenofovir
Lamivudine
Adefovir
Chronic Hepatitis B
Lead sponsor: Keimyung University Dongsan Medical Center
Sponsor class: OTHER
Collaborators: name: Kyungpook National University Hospital
name: Daegu Catholic University Medical Center
name: DongGuk University
name: Pusan National University Hospital
name: Yeungnam University Hospital
First posted: 2012-11-22
Enrollment: 171
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage number of patients with virus reactivation
timeFrame: Week 96 while on treatment
Secondary outcomes:
measure: Virologic response
timeFrame: Week 96 while on treatment
measure: Antiviral resistance
timeFrame: Week 96 while on treatment
measure: Biochemical response
timeFrame: Week 96 while on treatment
measure: Serologic response
timeFrame: Week 96 while on treatment
measure: Safety assessment
timeFrame: Week 96 while on treatment
Other outcomes:
Locations:
city: Daegu
country: Korea, Republic of
facility: Department of Internal Medicine, Keimyung University Dongsan Medical Center
Study officials:
affiliation: Department of Internal Medicine, Keimyung University Dongsan Medical Center
name: Byoung Kuk Jang, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee HJ, Kim SJ, Kweon YO, Park SY, Heo J, Woo HY, Hwang JS, Chung WJ, Lee CH, Kim BS, Suh JI, Tak WY, Jang BK. Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients. PLoS One. 2018 Jan 12;13(1):e0190581. doi: 10.1371/journal.pone.0190581. eCollection 2018.