Tenofovir vs. Tenofovir Plus Entecavir in Entecavir-Resistant Chronic Hepatitis B
Condition: Chronic Viral Hepatitis B Without Delta-agent
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis
Study type: Interventional
Phase: Phase 4

Summary: 
      With the availability of potent nucloes(t)ide analogues (NA), such as tenofovir disoproxil
      fumarate (TDF) and entecavir (ETV), suppression of serum HBV DNA to undetectable levels by
      polymerase chain reaction (PCR) assays became achievable in most NA treatment-naïve patients.
      Until recently, however, many patients commenced antiviral treatment with inferior NAs prior
      to the availability of TDF or ETV, such as lamivudine (LAM) which has a low genetic barrier
      to resistance.

      ETV resistance increase up to 51% of patients after 5 years of ETV treatment in
      lamivudine-refractory patients. Resistance to ETV appears to occur through a two-hit
      mechanism with initial selection of M204V/I mutation followed by amino acid substitutions at
      rtT184, rtS202, or rtM250.

      In vitro studies showed that ETV-resistant mutations are susceptible to TDF, but there are
      little clinical data on the efficacy of TDF monotherapy in patients with ETV-resistance.

      On the other hand, there was a retrospective cohort study reporting that, with the
      combination of TDF and ETV, most of patients became HBV DNA undetectable after median 6
      months of treatment. Probability of reaching complete HBV DNA suppression was not decreased
      in patients with ADV or ETV-resistance.

      Thus, there is no consistent treatment recommendation for patients with ETV-resistance.

      In this clinical trial, the investigators will clarify whether tenofovir monotherapy is as
      effective as tenofovir plus entecavir in inducing complete virologic response in CHB patients
      with genotypic resistance to ETV and partial virologic response to ongoing treatment.
    

Detailed description: 
      A multi-center randomized active-controlled open-label trial

        -  Patients will be randomly assigned 1:1 to receive tenofovir (300 mg/day) or tenofovir
           (300 mg/day) plus entecavir (1 mg/day) for 48 weeks.

        -  Because over 98% of Korean patients with CHB have HBV genotype C, HBV genotype will not
           determined or be regarded as a stratification factor.

        -  Patients' treatment information before randomization will be retrospectively
           collected.(DNA change, HBeAg status, HBsAg titre, ALT, and treatment duration. etc)

        -  Patients will be screened within 4 weeks before randomization to determine study
           eligibility.
    

Intervention name(s): Tenofovir; Tenofovir; Entecavir
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Tenofovir 300mg Daily Oral; Tenofovir 300mg Daily Oral; Entecavir 1 mg daily Oral
Other intervention name(s): Viread; Viread; Baraclude
Intervention MeSH terms: Tenofovir; Entecavir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Resistance of Entecavir