Tenofovir Disoproxil Fumarate vs. Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response to Entecavir (STEEP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01711567
Recruitment Status : Completed
First Posted : October 22, 2012
Last Update Posted : November 9, 2016
Gilead Sciences
Information provided by (Responsible Party):
Hyung Joon Yim, Korea University

October 17, 2012
October 22, 2012
November 9, 2016
April 2013
December 2015   (Final data collection date for primary outcome measure)
Virologic response rate at year 1 (12 months) (HBV DNA < 20 IU/mL) [ Time Frame: up to the end of year 1 (12 months) ]
Same as current
Complete list of historical versions of study NCT01711567 on Archive Site
-Degree of HBV DNA reduction, mean HBV DNA, biochemical and serologic response rates, resistance, and adverse events at year 1 [ Time Frame: up to the end of year 1 (12 months) ]
Same as current
Not Provided
Not Provided
Tenofovir Disoproxil Fumarate vs. Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response to Entecavir
Switching to Tenofovir Disoproxil Fumarate vs. Continuing Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response During Entecavir Therapy: STEEP 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.

The number of patients needed was calculated using PASS 2008. We hypothesized that two-thirds (65%) of the patients receiving TDF, and one-fifth (20%) of the patients receiving ETV, would achieve virologic response. We also assumed a 15% drop-out rate; thus, 22 patients were needed in each group to achieve 80% power to demonstrate a difference between the groups with a 5% level of significance.

The primary efficacy end point will be analyzed on a per-protocol basis, including only those patients who had completed the treatment schedule of study. In contrast, the intention-to-treat analysis will include all randomized subjects, even those dropped-out from the study before 12 months, as cases of treatment failure.

Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Chronic Hepatitis B
  • Drug: tenofovir
    tenofovir 300 mg qd
    Other Name: tenofovir (viread)
  • Drug: entecavir
    entecavir 0.5 mg qd
    Other Name: entecavir(baraclude) 0.5 mg qd
  • Active Comparator: entecavir
    standard drugs
    Intervention: Drug: entecavir
  • Active Comparator: tenofovir
    study drugs
    Intervention: Drug: tenofovir
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
November 2016
December 2015   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
19 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
Korea, Republic of
STEEP study
Not Provided
Not Provided
Hyung Joon Yim, Korea University
Korea University
Gilead Sciences
Principal Investigator: Hyung Joon Yim, M.D. Korea University
Korea University
November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP