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

Pusan National University Yangsan Hospital

Status and phase

Unknown

Phase 4

Conditions

Chronic Hepatitis B

Treatments

Drug: Telbivudine

Drug: Tenofovir

Drug: Entecavir

Study type

Interventional

Funder types

Other

Identifiers

NCT01588912

CLDT600AKR07T

Details and patient eligibility

About

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.

Full 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.

Enrollment

104 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No 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