Chronic Hepatitis B | Tenofovir Disoproxil Fumarate vs. Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response to Entecavir
Chronic Hepatitis B research study
What is the primary objective of this study?
Entecavir, a potent antiviral agent, has been widely used for treatment-naïve chronic hepatitis B patients. However, about 20% of patients showed partial virologic response after 2 year of entecavir therapy (33% in HBeAg positive, 10% in HBeAg negative patients). Tenofovir is a nucleotide analogue with more potent antiviral activity. In addition, there is no cross resistance between the two drugs. Therefore it is assumed that tenofovir would be effective in the treatment of chronic hepatitis B patients who shows partial virologic response (detectable HBV DNA by real time PCR after 12 months of treatment) despite treatment with entecavir. In this study, we will compare the efficacy of switching to tenofovir with continuing entecavir in patients who shows partial virologic response to entecavir.
Who is eligible to participate?
Inclusion Criteria: 1. CHB patients (positive HBsAg more than 6 months) 2. Age 19 years old 3. HBeAg positive or negative patients 4. Patients receiving entecavir 0.5 mg more than 12 months 5. Detectable HBV DNA by real time PCR (HBV > 60 IU/mL) 6. Compensated liver function (Child-Pugh-Turcotte score ≤7, prothrombin time 3 sec above ULN or INR ≤1.5, serum albumin >3 g/dL, total bilirubin <2.5 mg/dL, no history of variceal bleeding, diuretics or ascites requiring paracentesis, hepatic encephalopathy) Exclusion Criteria: 1. History of treatment with nucleotide analogue other than 0.5 mg of ETV 2. Serum creatinine level > 1.5 mg/dL or creatinine clearance < 50 mL/min 3. Absolute neutrophil count ≤ 1000 cell/mL 4. Hemoglobin level ≤ 10 g/dL in men or ≤ 9 g/dL in women 5. Antiviral resistance mutations on rtT184, rtS202, or rtM250 + rtM204V/I 6. A positive antibody test for human immunodeficiency virus, hepatitis C virus, or hepatitis D virus 7. Pregnancy or lactation 8. HCC (in cases where alfa-fetoprotein levels were over 100 ng/mL, abdominal computed tomography or magnetic resonance image was performed to exclude HCC) 9. Untreated malignancy other than HCC.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Chronic Hepatitis B
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:tenofovirtenofovir 300 mg qd
Drug:entecavirentecavir 0.5 mg qd
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Start Date: April 2013
Completed Date: November 2016
Phase: Phase 4
Primary Outcome: Virologic response rate at year 1 (12 months) (HBV DNA < 20 IU/mL)
Secondary Outcome: -Degree of HBV DNA reduction, mean HBV DNA, biochemical and serologic response rates, resistance, and adverse events at year 1
Study sponsors, principal investigator, and references
Principal Investigator: Hyung Joon Yim, M.D.
Lead Sponsor: Korea University
Collaborator: Gilead Sciences