Efficacy of Telbivudine With or Without add-on Tenofovir According to Roadmap Strategy Compare With Entecavir (TETRA)

April 30, 2012 updated by: Ki Tae Yoon, Pusan National University Yangsan Hospital

A Randomized, Prospective, Multicenter, Open-label Study to Evaluate the Efficacy of Telbivudine With or Without add-on Tenofovir According to Roadmap Strategy Compare With Entecavir in HBeAg-positive Chronic Hepatitis B Patients

Oral antiviral drugs which can be given to patients with HBeAg-positive chronic hepatitis B include Lamivudine, Clevudine, Adefovir, Telbivudine, Entecavir and Tenofovir. 2009 American Association for the Study of Liver Disease (AASLD) Treatment Guidelines and 2009 European association for the Study of the Liver (EASL) Treatment Guidelines recommend the administration of Entecavir or Tenofovir with high potency and low resistance. Lamivudine has low antiviral potency and high incidence of mutation in long-term administration compared to Entecavir or Tenofovir. Clevudine causes the elevated creatinine kinase (CK), side effects including myositis/myopathy and much mutation in the long-term administration. Globe study demonstrated Telbivudine had more excellent antiviral potency than Lamivudine, which was also comparable to or higher than Entecavir or Tenofovir. Nevertheless, the choice of treatment drugs can be limited due to the mutation rate of 25% for 2 years. However, the analysis of Globe study results showed that 2-year treatment progress was very good in patient who showed virologic response at 24 weeks after the initiation of treatment and that high antiviral potency and low mutation rate were observed when the Telbivudine roadmap strategy (in the event that virologic response is shown at 24 weeks, telbivudine monotherapy is maintained and in the event that virologic response is not shown, tenofovir add-on therapy is done) recently implemented and announced in 2011 Asian Pacific Association for the Study of the Liver (APASL) was applied. However, the study was single arm study, which restricted the comparison between Entecavir and Tenofovir monotherapy groups. Therefore, this study intends to compare the anti-viral effect and mutation rate between Entecavir 0.5mg monotherapy group and Telbivudine roadmap strategy group in patients with HBeAg-positive chronic hepatitis B through a randomized study.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

104 treatment-naïve patients with HBeAg-positive chronic hepatitis B who fulfill the inclusion criteria will be randomized in a 1:1 ratio to receive either Telbivudine 600mg monotherapy or Entecavir monotherapy with stratification before randomization according to presence of cirrhosis. For Telbivudine group, Telbivudine monotherapy or Tenofovir combined therapy will be done according to virologic response at 24 weeks and the primary study will be completed at Week 48 and treatment response will be analyzed. The treatment will be extended to Week 96 and the secondary analysis will be performed then.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
104

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Korea, Republic of
      • Busan, Korea, Republic of
        • Not yet recruiting
        • Byung Chul Yoon
        • Contact:
          • Byung Chul Yoon
        • Principal Investigator:
          • Byung Chul Yoon
      • Busan, Korea, Republic of
        • Not yet recruiting
        • Eun Uk Jung
        • Contact:
          • Eun Uk Jung
        • Principal Investigator:
          • Eun Uk Jung
      • Busan, Korea, Republic of
        • Not yet recruiting
        • Hyun Young Woo
        • Contact:
          • Hyun Young Woo
        • Principal Investigator:
          • Hyun Young Woo
      • Busan, Korea, Republic of
        • Not yet recruiting
        • Nae-Yun Heo
        • Contact:
          • Nae-Yun Heo
        • Principal Investigator:
          • Nae-Yun Heo
      • Busan, Korea, Republic of
        • Not yet recruiting
        • Yang Hyun Baek
        • Contact:
          • Yang Hyun Baek
        • Principal Investigator:
          • Yang Hyun Baek
      • Changwon, Korea, Republic of
        • Not yet recruiting
        • Hyun Jin Jo
        • Contact:
          • Hyun Jin Jo
        • Principal Investigator:
          • Hyun Jin Jo
      • Daegu, Korea, Republic of
        • Not yet recruiting
        • Byung Seok Kim
        • Contact:
          • Byung Seok Kim
        • Principal Investigator:
          • Byung Seok Kim
      • Daegu, Korea, Republic of
        • Not yet recruiting
        • Soo Young Park
        • Principal Investigator:
          • Soo Young Park
      • Jinju, Korea, Republic of
        • Not yet recruiting
        • Hyun Ju Min
        • Contact:
          • Hyun Ju Min
        • Principal Investigator:
          • Hyun Ju Min
      • Yangsan, Korea, Republic of
        • Recruiting
        • Ki Tae Yoon
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ki Tae Yoon, M.D.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female, at least 18 years of age
  • Documented CHB defined by HBsAg or HBeAg positive at least 6 month prior
  • HBsAg positive at screening visit
  • HBeAg positive and Anti-HBe negative at screening visit
  • Serum HBV DNA 20,000~200,000,000 IU/mL as determined by Realtime PCR at screening visit
  • Serum ALT 80~400 IU/mL at screening visit
  • Patient is willing and able to comply with the study drug regimen and all other study requirements
  • Patient is willing and able to provide written informed consent to participate in the study

Exclusion Criteria:

  • Patient has received interferon, pegylated interferon, nucleoside or nucleotide drugs at any time
  • Patient is co-infected with HCV, HDV, or HIV
  • Patient with Child Pugh B or C (Child Pugh score ≥ 7)
  • Patient has a history of or clinical signs/symptoms of hepatic decompensation such as ascites, esophageal variceal bleeding, hepatic encephalopathy
  • Patient has any of the following laboratory values at screening visit:
  • Hemoglobin <10 g/dL
  • Absolute neutrophil count (ANC) <1,500/mm3
  • Platelet count <70,000/mm3
  • Patient has a history of clinical and laboratory evidence of chronic renal insufficiency defined as an estimated serum creatinine clearance < 50 mL/min using the MDRD formula at screening visit
  • Patient is pregnant or breastfeeding
  • Patient with currently abusing illegal drugs or alcohol sufficient
  • Patient has organ transplantation
  • History of any other acute or chronic medical condition that in the opinion of the investigator would make the patient unsuitable for inclusion into the study
  • Patient has one or more additional known primary or secondary causes of liver disease, other than CHB, including steatohepatitis and autoimmune hepatitis
  • Patient, if AFP is >50ng/mL at screening visit, has image findings suggestive of HCC at Liver CT or Liver MRI
  • Patient with hypersensitivity for study drug

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Telbivudine-Tenofovir roadmap
Drug: Telbivudine
If virologic response, which means HBV DNA < 50 IU/mL, is shown at 24 weeks, telbivudine monotherapy is maintained and in the event that virologic response is not shown, tenofovir add-on therapy is done
Other Names:
  • Sebivo
Drug: Tenofovir
If virologic response, which means HBV DNA < 50 IU/mL, is shown at 24 weeks, telbivudine monotherapy is maintained and in the event that virologic response is not shown, tenofovir add-on therapy is done
Other Names:
  • Viread
Active Comparator: Entecavir
Drug: Entecavir
Maintain the entecavir through the study period
Other Names:
  • Baraclude

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
HBV DNA non-detectability
Time Frame: Week 48
Low detection limit of HBV DNA is 50 IU/mL
Week 48

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
HBV DNA non-detectability
Time Frame: Week 96
Low detection limit of HBV DNA is 50 IU/mL
Week 96
Reduction of HBV DNA from baseline
Time Frame: Week 12, 24, 36, 48, 60, 72, 84 & 96
Week 12, 24, 36, 48, 60, 72, 84 & 96
HBeAg loss or HBeAg seroconversion
Time Frame: Week 48 & 96
Week 48 & 96
HBsAg loss or HBsAg seroconversion
Time Frame: Week 48 & 96
Week 48 & 96
ALT normalization
Time Frame: Week 48 & 96
Week 48 & 96
Accumulate rate of Viral breakthrough
Time Frame: Week 48 & 96
Week 48 & 96
Accumulate rate of Biochemical Breakthrough
Time Frame: Week 48 & 96
Week 48 & 96
Accumulate rate of genotypic mutation in HBV
Time Frame: Week 48 & 96
Week 48 & 96
Change of eGFR from baseline
Time Frame: Week 12, 24, 36, 48, 60, 72, 84 & 96
Week 12, 24, 36, 48, 60, 72, 84 & 96
Accumulate rate of CK abnormal elevation
Time Frame: Week 48 & 96
Week 48 & 96
Accumulate rate of symptom related muscular disease
Time Frame: Week 48 & 96
Week 48 & 96
Accumulate rate of Adverse event or serious adverse event
Time Frame: Week 48 & 96
Week 48 & 96

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pusan National University Yangsan Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ki Tae Yoon, M.D., Pusan National University Yangsan Hospital

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2012

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2013

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 27, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 27, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 1, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 2, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 30, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CLDT600AKR07T

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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