Efficacy of Telbivudine With or Without add-on Tenofovir According to Roadmap Strategy Compare With Entecavir
Information source: Pusan National University Yangsan Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic Hepatitis B
Intervention: Telbivudine (Drug); Tenofovir (Drug); Entecavir (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Pusan National University Yangsan Hospital Official(s) and/or principal investigator(s): Ki Tae Yoon, M.D., Principal Investigator, Affiliation: Pusan National University Yangsan Hospital
Overall contact: Ki Tae Yoon, M.D., Phone: 82-55-360-2362, Email: ktyoon@pusan.ac.kr
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.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: HBV DNA non-detectability
Secondary outcome: HBV DNA non-detectabilityReduction 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
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Ki Tae Yoon, M.D., Phone: 82-55-360-2362, Email: ktyoon@pusan.ac.kr
Byung Chul Yoon, Busan, Korea, Republic of; Not yet recruiting Byung Chul Yoon Byung Chul Yoon, Principal Investigator
Eun Uk Jung, Busan, Korea, Republic of; Not yet recruiting Eun Uk Jung Eun Uk Jung, Principal Investigator
Hyun Young Woo, Busan, Korea, Republic of; Not yet recruiting Hyun Young Woo Hyun Young Woo, Principal Investigator
Nae-Yun Heo, Busan, Korea, Republic of; Not yet recruiting Nae-Yun Heo Nae-Yun Heo, Principal Investigator
Yang Hyun Baek, Busan, Korea, Republic of; Not yet recruiting Yang Hyun Baek Yang Hyun Baek, Principal Investigator
Hyun Jin Jo, Changwon, Korea, Republic of; Not yet recruiting Hyun Jin Jo Hyun Jin Jo, Principal Investigator
Byung Seok Kim, Daegu, Korea, Republic of; Not yet recruiting Byung Seok Kim Byung Seok Kim, Principal Investigator
Soo Young Park, Daegu, Korea, Republic of; Not yet recruiting Soo Young Park Soo Young Park, Principal Investigator
Hyun Ju Min, Jinju, Korea, Republic of; Not yet recruiting Hyun Ju Min Hyun Ju Min, Principal Investigator
Ki Tae Yoon, Yangsan, Korea, Republic of; Recruiting Ki Tae Yoon, M.D., Phone: 82-55-360-2362, Email: ktyoon@pusan.ac.kr Surin Tak, Phone: 82-55-360-1738, Email: surintak@hanmail.net Ki Tae Yoon, M.D., Principal Investigator
Additional Information
Starting date: April 2012
Last updated: April 30, 2012
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