Adding Adefovir Dipivoxil Versus Switching to Entecavir in Patients With Lamivudine-resistant Chronic Hepatitis B
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Study type: Interventional
Phase: Phase 4

Summary: 
      Antiviral resistance mutations limit the efficacy of therapy for chronic hepatitis B. At year
      2, resistance to adefovir may occur as high as 25% in patients with history of lamivudine
      resistance. Resistance to entecavir is reported to be 10% in lamivudine refractory patients
      during the same period. However, combination of lamivudine and adefovir decreased the
      adefovir resistance rate as low as 0% in the recent studies. By overcoming the antiviral
      resistance, the efficacy of therapy will be maximized. This study is intended to compare the
      efficacy of two strategies, combination of lamivudine and adefovir vs. entecavir monotherapy
      in patients with lamivudine resistance.
    

Detailed description: 
      Recently, published data showed combination of lamivudine and adefovir lead to PCR negativity
      (<1000 copies/mL) up to 80% in the treatment of lamivudine-resistant chronic hepatitis B at
      year 2 [Rapti et al. Hepatology 2007 Feb;45(2):307-13.]. Other studies also showed 76% and
      69% PCR negativity in mostly HBeAg negative subjects [Lampertico et al. Hepatology 2006
      Oct;44(4) Suppl 1:556A-557A, Lampertico et al. Hepatology 2006 Oct;44(4) Suppl 1:693A-694A].

      In the study for the treatment of lamivudine-resistant chronic hepatitis B patients which
      included HBeAg positive subjects more predominantly, entecavir monotherapy showed 34% of PCR
      negativity (<300 copies/mL) at year 2 [Tenney DJ, et al. Antimicrob Agents Chemother. 2007
      Mar;51(3):902-11].

      Although it is assumed that combination of lamivudine and adefovir would be more effective
      than entecavir monotherapy for lamivudine resistant patients, we cannot verify the
      assumption, because there is no data directly comparing these two strategies until now.

      The aim of this study is to determine the most effective therapy for the patients with
      lamivudine resistant chronic hepatitis B. We will compare the PCR negativity (<60 IU/ml) of
      HBV DNA at year 2 in patients receiving 'the combination of lamivudine and adefovir' and
      'entecavir monotherapy'.

      Since we are planning to include lamivudine-resistant chronic hepatitis B patients regardless
      of HBeAg status, we assumed the PCR negativity (<300 copies/mL or <60 IU/mL) in
      adefovir-lamivudine combination and entecavir monotherapy group as 55% and 34%, respectively,
      considering HBeAg status and lower detection limit of PCR.

      The result of this study will be able to clearly demonstrate the superiority of combination
      therapy with lamivudine and adefovir to entecavir monotherapy, which provide us the guide to
      rescue therapy for patients with lamivudine resistant HBV.
    

Intervention name(s): combination of lamivudine+adefovir vs entecavir
Intervention type(s): Drug
Intervention description(s): Lamivudine 100 mg/day, Adefovir 10 mg/day, Entecavir 0.5 mg/day
Other intervention name(s): Zeffix, Hepsera, Baraclude
Intervention MeSH terms: Lamivudine; Adefovir; Entecavir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: lamivudine resistant mutations; rescue therapy