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

Primary Purpose

Chronic Hepatitis B

Status
Unknown status
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Telbivudine
Tenofovir
Entecavir
Sponsored by
Pusan National University Yangsan Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring chronic hepatitis B, HBeAg positive, telbivudine, tenofovir, entecavir, roadmap

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Byung Chul Yoon
  • Eun Uk Jung
  • Hyun Young Woo
  • Nae-Yun Heo
  • Yang Hyun Baek
  • Hyun Jin Jo
  • Byung Seok Kim
  • Soo Young Park
  • Hyun Ju Min
  • Ki Tae YoonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Telbivudine-Tenofovir roadmap

Entecavir

Arm Description

Outcomes

Primary Outcome Measures

HBV DNA non-detectability
Low detection limit of HBV DNA is 50 IU/mL

Secondary Outcome Measures

HBV DNA non-detectability
Low detection limit of HBV DNA is 50 IU/mL
Reduction of HBV DNA from baseline
HBeAg loss or HBeAg seroconversion
HBsAg loss or HBsAg seroconversion
ALT normalization
Accumulate rate of Viral breakthrough
Accumulate rate of Biochemical Breakthrough
Accumulate rate of genotypic mutation in HBV
Change of eGFR from baseline
Accumulate rate of CK abnormal elevation
Accumulate rate of symptom related muscular disease
Accumulate rate of Adverse event or serious adverse event

Full Information

First Posted
April 27, 2012
Last Updated
April 30, 2012
Sponsor
Pusan National University Yangsan Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01588912
Brief Title
Efficacy of Telbivudine With or Without add-on Tenofovir According to Roadmap Strategy Compare With Entecavir
Acronym
TETRA
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2012
Overall Recruitment Status
Unknown status
Study Start Date
April 2012 (undefined)
Primary Completion Date
December 2013 (Anticipated)
Study Completion Date
December 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Pusan National University Yangsan Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
chronic hepatitis B, HBeAg positive, telbivudine, tenofovir, entecavir, roadmap

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
104 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Telbivudine-Tenofovir roadmap
Arm Type
Experimental
Arm Title
Entecavir
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Telbivudine
Other Intervention Name(s)
Sebivo
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Tenofovir
Other Intervention Name(s)
Viread
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Entecavir
Other Intervention Name(s)
Baraclude
Intervention Description
Maintain the entecavir through the study period
Primary Outcome Measure Information:
Title
HBV DNA non-detectability
Description
Low detection limit of HBV DNA is 50 IU/mL
Time Frame
Week 48
Secondary Outcome Measure Information:
Title
HBV DNA non-detectability
Description
Low detection limit of HBV DNA is 50 IU/mL
Time Frame
Week 96
Title
Reduction of HBV DNA from baseline
Time Frame
Week 12, 24, 36, 48, 60, 72, 84 & 96
Title
HBeAg loss or HBeAg seroconversion
Time Frame
Week 48 & 96
Title
HBsAg loss or HBsAg seroconversion
Time Frame
Week 48 & 96
Title
ALT normalization
Time Frame
Week 48 & 96
Title
Accumulate rate of Viral breakthrough
Time Frame
Week 48 & 96
Title
Accumulate rate of Biochemical Breakthrough
Time Frame
Week 48 & 96
Title
Accumulate rate of genotypic mutation in HBV
Time Frame
Week 48 & 96
Title
Change of eGFR from baseline
Time Frame
Week 12, 24, 36, 48, 60, 72, 84 & 96
Title
Accumulate rate of CK abnormal elevation
Time Frame
Week 48 & 96
Title
Accumulate rate of symptom related muscular disease
Time Frame
Week 48 & 96
Title
Accumulate rate of Adverse event or serious adverse event
Time Frame
Week 48 & 96

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ki Tae Yoon, M.D.
Phone
82-55-360-2362
Email
ktyoon@pusan.ac.kr
First Name & Middle Initial & Last Name or Official Title & Degree
Surin Tak
Phone
82-55-360-1738
Email
surintak@hanmail.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ki Tae Yoon, M.D.
Organizational Affiliation
Pusan National University Yangsan Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Byung Chul Yoon
City
Busan
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Byung Chul Yoon
First Name & Middle Initial & Last Name & Degree
Byung Chul Yoon
Facility Name
Eun Uk Jung
City
Busan
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eun Uk Jung
First Name & Middle Initial & Last Name & Degree
Eun Uk Jung
Facility Name
Hyun Young Woo
City
Busan
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hyun Young Woo
First Name & Middle Initial & Last Name & Degree
Hyun Young Woo
Facility Name
Nae-Yun Heo
City
Busan
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nae-Yun Heo
First Name & Middle Initial & Last Name & Degree
Nae-Yun Heo
Facility Name
Yang Hyun Baek
City
Busan
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yang Hyun Baek
First Name & Middle Initial & Last Name & Degree
Yang Hyun Baek
Facility Name
Hyun Jin Jo
City
Changwon
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hyun Jin Jo
First Name & Middle Initial & Last Name & Degree
Hyun Jin Jo
Facility Name
Byung Seok Kim
City
Daegu
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Byung Seok Kim
First Name & Middle Initial & Last Name & Degree
Byung Seok Kim
Facility Name
Soo Young Park
City
Daegu
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Soo Young Park
First Name & Middle Initial & Last Name & Degree
Soo Young Park
Facility Name
Hyun Ju Min
City
Jinju
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hyun Ju Min
First Name & Middle Initial & Last Name & Degree
Hyun Ju Min
Facility Name
Ki Tae Yoon
City
Yangsan
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ki Tae Yoon, M.D.
Phone
82-55-360-2362
Email
ktyoon@pusan.ac.kr
First Name & Middle Initial & Last Name & Degree
Surin Tak
Phone
82-55-360-1738
Email
surintak@hanmail.net
First Name & Middle Initial & Last Name & Degree
Ki Tae Yoon, M.D.

12. IPD Sharing Statement

Learn more about this trial

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

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