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

This study has been completed.
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Hyung Joon Yim, Korea University
ClinicalTrials.gov Identifier:
NCT01711567
First received: October 17, 2012
Last updated: November 8, 2016
Last verified: November 2016
  Purpose
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.

Condition Intervention Phase
Chronic Hepatitis B
Drug: tenofovir
Drug: entecavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Switching to Tenofovir Disoproxil Fumarate vs. Continuing Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response During Entecavir Therapy: STEEP Study

Resource links provided by NLM:


Further study details as provided by Korea University:

Primary Outcome Measures:
  • Virologic response rate at year 1 (12 months) (HBV DNA < 20 IU/mL) [ Time Frame: up to the end of year 1 (12 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • -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) ] [ Designated as safety issue: Yes ]

Enrollment: 60
Study Start Date: April 2013
Study Completion Date: November 2016
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: entecavir
standard drugs
Drug: entecavir
entecavir 0.5 mg qd
Other Name: entecavir(baraclude) 0.5 mg qd
Active Comparator: tenofovir
study drugs
Drug: tenofovir
tenofovir 300 mg qd
Other Name: tenofovir (viread)

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.

  Eligibility

Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01711567

Locations
Korea, Republic of
Korea University Ansan Hospital
Ansan, Gyeonggi-do, Korea, Republic of, 425-707
Sponsors and Collaborators
Korea University
Gilead Sciences
Investigators
Principal Investigator: Hyung Joon Yim, M.D. Korea University
  More Information

Responsible Party: Hyung Joon Yim, Associate professor, Korea University
ClinicalTrials.gov Identifier: NCT01711567     History of Changes
Other Study ID Numbers: STEEP study 
Study First Received: October 17, 2012
Last Updated: November 8, 2016
Health Authority: Korea: Food and Drug Administration

Keywords provided by Korea University:
Chronic Hepatitis B
TENOFOVIR
ENTECAVIR
PARTIAL RESPONDER

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Entecavir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on December 09, 2016