A Randomized Controlled Trial on the Efficacy of Tenofovir Disoproxil Fumarate (TDF)-Switch Therapy in Chronic Hepatitis B Patients With Incomplete Response to Entecavir
Condition: Chronic Heptitis B
Study type: Interventional

Summary: 
      Currently, five nucleos(t)ide analogs are approved for the treatment of chronic hepatitis B,
      namely lamivudine, adefovir dipivoxil, telbivudine, entecavir (ETV) and tenofovir disoproxil
      fumarate (TDF). ETV and TDF are recommended as first-line therapy by all regional guidelines
      due to their high anti-viral potency and low risk of inducing resistance.

      ETV monotherapy for chronic HBV infection is highly effective in both HBeAg-positive and
      negative treatment-naïve patients. The cumulative probability of maintained virologic
      suppression with undetectable HBV DNA at year 1, 2 and 3 were 76.5%, 83.0% and 88.3%
      respectively.

      TDF is another potent anti-viral treatment for chronic hepatitis B. Up to 72% and 87% of
      HBeAg-positive and -negative patients achieved undetectable HBV DNA by week 144 of TDF
      monotherapy. It is also effective in patients with prior exposure to other nucleo(s)tide
      analogs. Previous studies demonstrated that TDF can be used as an effective rescue therapy in
      lamivudine or adefovir-treated patients with incomplete virologic response.

      However, the optimal treatment for patients with suboptimal response to ETV is uncertain.
      With this background, we will conduct a randomized controlled trial to evaluate the efficacy
      of TDF switch therapy in patients with incomplete virologic response to ETV treatment.
    

Detailed description: 
      Chronic hepatitis B virus (HBV) infection affects approximately 400 million people worldwide,
      and three-quarter of them are from Asia-Pacific region [1-3]. Nucleos(t)ide analogs treatment
      can suppress viral replication, delay cirrhotic complications and reduce the risk of
      hepatocellular carcinoma (HCC) [4-5].

      Currently, five nucleos(t)ide analogs are approved for the treatment of chronic hepatitis B,
      namely lamivudine, adefovir dipivoxil, telbivudine, entecavir (ETV) and tenofovir disoproxil
      fumarate (TDF). ETV and TDF are recommended as first-line therapy by all regional guidelines
      due to their high anti-viral potency and low risk of inducing resistance [6-8].

      ETV monotherapy for chronic HBV infection is highly effective in both HBeAg-positive and
      negative treatment-naïve patients [9-10]. The cumulative probability of maintained virologic
      suppression with undetectable HBV DNA at year 1, 2 and 3 were 76.5%, 83.0% and 88.3%
      respectively [11].

      TDF is another potent anti-viral treatment for chronic hepatitis B. Up to 72% and 87% of
      HBeAg-positive and -negative patients achieved undetectable HBV DNA by week 144 of TDF
      monotherapy [12]. It is also effective in patients with prior exposure to other nucleo(s)tide
      analogs. Previous studies demonstrated that TDF can be used as an effective rescue therapy in
      lamivudine or adefovir-treated patients with incomplete virologic response [13-14].

      The importance of complete viral suppression should be emphasized. In treatment-naïve
      patients, there is a positive correlation between HBV DNA level with risk of developing
      cirrhosis and HCC [15-17]. In a recent report on 372 ETV-treated patients, suppression of HBV
      DNA to less than 2000 IU/ml was associated with lower risk of disease progression among those
      with cirrhosis at baseline [18]. Therefore, suppressing HBV DNA to undetectable level should
      be the treatment target, especially in patients with established cirrhosis who are at the
      greatest risk of HCC.
    

Intervention name(s): tenofovir disoproxil fumarate; Entecavir
Intervention type(s): Drug; Drug
Intervention MeSH terms: Tenofovir; Entecavir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment