Chronic Hepatitis BPhase 4TETRANCT01588912
Efficacy of Telbivudine With or Without add-on Tenofovir According to Roadmap Strategy Compare With Entecavir
A Phase 4 study testing Telbivudine, Tenofovir and Entecavir in people with Chronic Hepatitis B, run by Pusan National University Yangsan Hospital at 10 sites in South Korea.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Telbivudine, Tenofovir and Entecavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 10 sitesSouth Korea
- Study dates
- Apr 2012to Dec 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
South Korea10 sites, 10 recruiting
- Not yet recruiting
Byung Chul Yoon
Busan
Byung Chul Yoon
Byung Chul Yoon
- Not yet recruiting
Eun Uk Jung
Busan
Eun Uk Jung
Eun Uk Jung
- Not yet recruiting
Hyun Young Woo
Busan
Hyun Young Woo
Hyun Young Woo
- Not yet recruiting
Nae-Yun Heo
Busan
Nae-Yun Heo
Nae-Yun Heo
- Not yet recruiting
Yang Hyun Baek
Busan
Yang Hyun Baek
Yang Hyun Baek
- Not yet recruiting
Hyun Jin Jo
Changwon
Hyun Jin Jo
Hyun Jin Jo
- Not yet recruiting
Byung Seok Kim
Daegu
Byung Seok Kim
Byung Seok Kim
- Not yet recruiting
Soo Young Park
Daegu
Soo Young Park
Soo Young Park
- Not yet recruiting
Hyun Ju Min
Jinju
Hyun Ju Min
Hyun Ju Min
- Recruiting
Ki Tae Yoon
Yangsan
Ki Tae Yoon, M.D., 82-55-360-2362, ktyoon@pusan.ac.kr
Surin Tak, 82-55-360-1738, surintak@hanmail.net
About this study
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
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.
Read the 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.
- Conditions
- Chronic Hepatitis B
- Being tested
- Telbivudine, Tenofovir, Entecavir
- Keywords
- chronic hepatitis B, HBeAg positive, telbivudine, tenofovir, entecavir, roadmap
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TelbivudineDrug
Also called Sebivo
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
TenofovirDrug
Also called Viread
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
EntecavirDrug
Also called Baraclude
Maintain the entecavir through the study period
| Study group | Role | What they receive |
|---|---|---|
| Telbivudine-Tenofovir roadmap | Experimental | Not described Receives: Drug: Telbivudine; Drug: Tenofovir |
| Entecavir | Active comparator | Not described Receives: Drug: Entecavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
HBV DNA non-detectability
Low detection limit of HBV DNA is 50 IU/mL
Measured: Week 48
Secondary outcomes (12)
HBV DNA non-detectability
Low detection limit of HBV DNA is 50 IU/mL
Measured: Week 96
Reduction of HBV DNA from baseline
Measured: Week 12, 24, 36, 48, 60, 72, 84 & 96
HBeAg loss or HBeAg seroconversion
Measured: Week 48 & 96
HBsAg loss or HBsAg seroconversion
Measured: Week 48 & 96
ALT normalization
Measured: Week 48 & 96
Accumulate rate of Viral breakthrough
Measured: Week 48 & 96
Accumulate rate of Biochemical Breakthrough
Measured: Week 48 & 96
Accumulate rate of genotypic mutation in HBV
Measured: Week 48 & 96
Change of eGFR from baseline
Measured: Week 12, 24, 36, 48, 60, 72, 84 & 96
Accumulate rate of CK abnormal elevation
Measured: Week 48 & 96
Accumulate rate of symptom related muscular disease
Measured: Week 48 & 96
Accumulate rate of Adverse event or serious adverse event
Measured: Week 48 & 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2012 (estimated)
- Study startApr 2012
- Primary completionDec 2013 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pusan National University Yangsan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ki Tae Yoon, Pusan National University Yangsan Hospital
- Investigators
- Ki Tae Yoon, M.D., Principal investigator, Pusan National University Yangsan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01588912
- Sponsor's protocol ID
- CLDT600AKR07T
- Acronym
- TETRA
- Status last verified
- Apr 2012
- First submitted
- 27 Apr 2012
- Last updated
- 2 May 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01588912
- Acronym / sponsor ID
- TETRA / CLDT600AKR07T
- Conditions
- Chronic Hepatitis B
- Keywords
- chronic hepatitis B, HBeAg positive, telbivudine, tenofovir, entecavir, roadmap
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- Pusan National University Yangsan HospitalUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 1 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Telbivudine-Tenofovir roadmap | Experimental | Drug: Telbivudine, Drug: Tenofovir |
| Entecavir | Active comparator | Drug: Entecavir |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (16 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TelbivudineAlso: SebivoIf 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 | Drug | Telbivudine-Tenofovir roadmap |
| TenofovirAlso: VireadIf 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 | Drug | Telbivudine-Tenofovir roadmap |
| EntecavirAlso: BaracludeMaintain the entecavir through the study period | Drug | Entecavir |
Primary outcome
HBV DNA non-detectability
Time frame: Week 48
Low detection limit of HBV DNA is 50 IU/mL
12 secondary outcomes
HBV DNA non-detectability
Time frame: Week 96
Reduction of HBV DNA from baseline
Time frame: Week 12, 24, 36, 48, 60, 72, 84 & 96
HBeAg loss or HBeAg seroconversion
Time frame: Week 48 & 96
HBsAg loss or HBsAg seroconversion
Time frame: Week 48 & 96
ALT normalization
Time frame: Week 48 & 96
Accumulate rate of Viral breakthrough
Time frame: Week 48 & 96
Accumulate rate of Biochemical Breakthrough
Time frame: Week 48 & 96
Accumulate rate of genotypic mutation in HBV
Time frame: Week 48 & 96
Change of eGFR from baseline
Time frame: Week 12, 24, 36, 48, 60, 72, 84 & 96
Accumulate rate of CK abnormal elevation
Time frame: Week 48 & 96
Accumulate rate of symptom related muscular disease
Time frame: Week 48 & 96
Accumulate rate of Adverse event or serious adverse event
Time frame: Week 48 & 96
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ki Tae Yoon, M.D. principal investigator
Pusan National University Yangsan Hospital
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Telbivudine, Tenofovir and Entecavir in people with Chronic Hepatitis B, run by Pusan National University Yangsan Hospital at 10 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ki Tae Yoon, M.D. (82-55-360-2362, ktyoon@pusan.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HBV DNA non-detectability (time frame: Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2012.