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

November 8, 2016 updated by: Hyung Joon Yim, Korea University

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
    • Gyeonggi-do
      • Ansan, Gyeonggi-do, Korea, Republic of, 425-707
        • Korea University Ansan Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: entecavir
standard drugs
Drug: entecavir
entecavir 0.5 mg qd
Other Names:
  • entecavir(baraclude) 0.5 mg qd
Active Comparator: tenofovir
study drugs
Drug: tenofovir
tenofovir 300 mg qd
Other Names:
  • tenofovir (viread)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Virologic response rate at year 1 (12 months) (HBV DNA < 20 IU/mL)
Time Frame: up to the end of year 1 (12 months)
up to the end of year 1 (12 months)

Secondary Outcome Measures

Outcome Measure
Time Frame
-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)
up to the end of year 1 (12 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Korea University

Collaborators

Gilead Sciences

Investigators

  • Principal Investigator: Hyung Joon Yim, M.D., Korea University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

November 1, 2016

Study Registration Dates

First Submitted

October 17, 2012

First Submitted That Met QC Criteria

October 18, 2012

First Posted (Estimate)

October 22, 2012

Study Record Updates

Last Update Posted (Estimate)

November 9, 2016

Last Update Submitted That Met QC Criteria

November 8, 2016

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STEEP study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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