Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified April 2012 by Pusan National University Yangsan Hospital.
Recruitment status was:  Recruiting
Sponsor:
Information provided by (Responsible Party):
Ki Tae Yoon, Pusan National University Yangsan Hospital
ClinicalTrials.gov Identifier:
NCT01588912
First received: April 27, 2012
Last updated: April 30, 2012
Last verified: April 2012
  Purpose
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.

Condition Intervention Phase
Chronic Hepatitis B
Drug: Telbivudine
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: 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

Resource links provided by NLM:


Further study details as provided by Pusan National University Yangsan Hospital:

Primary Outcome Measures:
  • HBV DNA non-detectability [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Low detection limit of HBV DNA is 50 IU/mL


Secondary Outcome Measures:
  • HBV DNA non-detectability [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Low detection limit of HBV DNA is 50 IU/mL

  • Reduction of HBV DNA from baseline [ Time Frame: Week 12, 24, 36, 48, 60, 72, 84 & 96 ] [ Designated as safety issue: No ]
  • HBeAg loss or HBeAg seroconversion [ Time Frame: Week 48 & 96 ] [ Designated as safety issue: No ]
  • HBsAg loss or HBsAg seroconversion [ Time Frame: Week 48 & 96 ] [ Designated as safety issue: No ]
  • ALT normalization [ Time Frame: Week 48 & 96 ] [ Designated as safety issue: No ]
  • Accumulate rate of Viral breakthrough [ Time Frame: Week 48 & 96 ] [ Designated as safety issue: No ]
  • Accumulate rate of Biochemical Breakthrough [ Time Frame: Week 48 & 96 ] [ Designated as safety issue: No ]
  • Accumulate rate of genotypic mutation in HBV [ Time Frame: Week 48 & 96 ] [ Designated as safety issue: No ]
  • Change of eGFR from baseline [ Time Frame: Week 12, 24, 36, 48, 60, 72, 84 & 96 ] [ Designated as safety issue: No ]
  • Accumulate rate of CK abnormal elevation [ Time Frame: Week 48 & 96 ] [ Designated as safety issue: Yes ]
  • Accumulate rate of symptom related muscular disease [ Time Frame: Week 48 & 96 ] [ Designated as safety issue: Yes ]
  • Accumulate rate of Adverse event or serious adverse event [ Time Frame: Week 48 & 96 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 104
Study Start Date: April 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Viread
Active Comparator: Entecavir Drug: Entecavir
Maintain the entecavir through the study period
Other Name: Baraclude

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01588912

Locations
Korea, Republic of
Byung Chul Yoon
Busan, Korea, Republic of
Eun Uk Jung
Busan, Korea, Republic of
Hyun Young Woo
Busan, Korea, Republic of
Nae-Yun Heo
Busan, Korea, Republic of
Yang Hyun Baek
Busan, Korea, Republic of
Hyun Jin Jo
Changwon, Korea, Republic of
Byung Seok Kim
Daegu, Korea, Republic of
Soo Young Park
Daegu, Korea, Republic of
Hyun Ju Min
Jinju, Korea, Republic of
Ki Tae Yoon
Yangsan, Korea, Republic of
Sponsors and Collaborators
Pusan National University Yangsan Hospital
Investigators
Principal Investigator: Ki Tae Yoon, M.D. Pusan National University Yangsan Hospital
  More Information

Responsible Party: Ki Tae Yoon, Assistant Professor, Pusan National University Yangsan Hospital
ClinicalTrials.gov Identifier: NCT01588912     History of Changes
Other Study ID Numbers: CLDT600AKR07T 
Study First Received: April 27, 2012
Last Updated: April 30, 2012
Health Authority: Korea: Food and Drug Administration

Keywords provided by Pusan National University Yangsan Hospital:
chronic hepatitis B
HBeAg positive
telbivudine
tenofovir
entecavir
roadmap

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
Telbivudine
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 05, 2016