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

• Status: Completed
• Trial end date: 2017-01-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Chinese University of Hong Kong
• Treatments: Entecavir; Tenofovir

Criteria

Inclusion Criteria:

• Age 18 or above

• Positive hepatitis B surface antigen for at least 6 months

• On ETV monotherapy as anti-viral treatment for at least 52 weeks

• HBV DNA (>20 IU/ml) at week 52 or more of ETV treatment

• Written informed consent obtained

Exclusion Criteria:

• Concurrent use of other antiviral treatment (including oral nucleos(t)ide analogs, interferon or pegylated interferon) for chronic hepatitis B.

• Concurrent use of steroids or immunosuppressive agents more than two week consecutively

• Co-infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV).

• Features suggestive of concomitant chronic liver diseases: positive anti-nuclear antibody (ANA) titer above 1/160, positive anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (SMA), abnormal serum ceruloplasmin or iron profile, or histological features of alternative chronic liver disease

• Pregnancy or breast feeding.

• Inability or unwillingness to give informed consent or abide by the requirements of the study.

• History of other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.

• Patients with baseline significant impaired renal function with creatinine clearance <30 ml/min or receiving dialysis for end stage renal disease.