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Comparison of Telbivudine Plus Adefovir With Lamivudine Plus Adefovir for the Treatment of Lamivudine-resistant Chronic Hepatitis B at 52 Weeks: A Pilot Study (TeSLA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01804387
Recruitment Status : Unknown
Verified March 2013 by Hyung Joon Yim, Korea University.
Recruitment status was:  Recruiting
First Posted : March 5, 2013
Last Update Posted : March 5, 2013
Information provided by (Responsible Party):
Hyung Joon Yim, Korea University

Brief Summary:
Lamivudine had been widely used for treatment-naïve chronic hepatitis B patients. However, development of antiviral resistance has been known as the major drawback: Incidence of lamivudine resistance was reported to be approximately 70% after 5 years (Lok AS et al, 2003). For the treatment of lamivudine resistance, adefovir has been widely used (Lok AS and McMahon B, 2009). However, switching to adefovir monotherapy was also reported to be at high risk of resistance, 25% at year 2 (Yeon JE et al, 2006). Recently, adding adefovir on lamivudine was shown to be superior to switching to adefovir monotherapy by decreasing the adefovir resistance (Rapti I et al, 2007, Lampertico P et al, 2007). However, combination of adefovir and lamivudine does not increase antiviral activity compared with adefovir monotherapy in patients with lamivudine resistance (Peters MG et al, 2004). As many patients are still viremic with the treatment of lamivudine and adefovir over 1 year, the investigators need more potent combination of the drugs. Telbivudine is a new nucleoside analogue with potent antiviral activity. The previous phase III study has shown the superiority of telbivudine over lamivudine in HBeAg positive and negative subjects (Lai CL et al, 2007). Therefore, telbivudine plus adefovir may be a better treatment option than lamivudine plus adefovir for the lamivudine-resistant chronic hepatitis B patients. No study assessing the efficacy of telbivudine plus adefovir has been conducted for these patients. The aim of this study is to evaluate the safety and efficacy of telbivudine plus adefovir compared with lamivudine plus adefovir in lamivudine resistant chronic hepatitis B patients at the end of 1 year follow-up,

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: telbivudine plus adefovir Drug: lamivudine plus adefovir Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparison of Telbivudine Plus Adefovir With Lamivudine Plus Adefovir for the Treatment of Lamivudine-resistant Chronic Hepatitis B at 52 Weeks: A Pilot Study
Study Start Date : May 2011
Estimated Primary Completion Date : December 2013
Estimated Study Completion Date : May 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Telbivudine plus adefovir
study drugs
Drug: telbivudine plus adefovir
telbivudine 600 mg qd plus adefovir 10 mg qd
Other Names:
  • telbivudine (sevibo)
  • adefovir (hepsera)

Active Comparator: Lamivudine plus adefovir
standard drugs
Drug: lamivudine plus adefovir
lamivudine 100 mg qd plus adefovir 10mg qd
Other Names:
  • lamivudine (zeffix)
  • adefovir (hepsera)

Primary Outcome Measures :
  1. The mean reduction of serum HBV DNA from the baseline at week 52. [ Time Frame: up to the end of year 1 (52 weeks) ]

Secondary Outcome Measures :
  1. HBV DNA undetectability(<20 IU/mL) [ Time Frame: up to the end of year 1 (52 weeks) ]
    At the end of year 1 in the two groups, HBV DNA undetectability by real time PCR will be assessed.

  2. mean serum HBV DNA level [ Time Frame: up to the end of year 1 (52 weeks) ]
  3. rate of ALT normalization [ Time Frame: up to the end of year 1 (52 weeks) ]
  4. rates of HBeAg loss [ Time Frame: up to the end of year 1 (52 weeks) ]
  5. rate of HBeAg seroconversion at week 52. [ Time Frame: up to the end of year 1 (52 weeks) ]

Other Outcome Measures:
  1. Antiviral resistance rate [ Time Frame: up to the end of year 1 (52 weeks) ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. HBeAg positive or negative chronic hepatitis B patients (positive HBsAg more than 6 months)
  2. Age ≥ 18 years old, and ≤70 years old
  3. Previous treatment with lamivudine more than 6 months
  4. Being on lamivudine at the time of screening
  5. Confirmed genotypic resistance to lamivudine by RFMP (rtM204V or I)
  6. Presence of virologic breakthrough ≥1 log increase of HBV DNA above na dir)
  7. HBV DNA ≥ 20,000 IU/mL
  8. Patient willing to give an informed consent (If patient is <20 years old, the parent or legal guardian also need to give an informed consent)

Exclusion Criteria:

  1. Out of inclusion criteria
  2. Presence of adefovir resistance (rtA181T or V, rtN236T) by RFMP assay
  3. Laboratory abnormalities as follows at screening: AFP>100 ng/mL, serum phosphorous level<2.4 mg/dL, serum creatinine level> 1.5 mg/dL or creatinine clearance < 50 mL/min
  4. Patient with a history of decompensated liver disease: Any patients with a history of ascites, hepatic encephalopathy, variceal bleeding, jaundice, or CTP>7 points should be excluded.
  5. History of treatment with nucleos(t)ide analogues other than lamivudine more than 4 weeks
  6. History of immune modulatory drugs (interferon, thymosin-alfa) within 24 weeks of screening
  7. Liver transplant patient
  8. Patient co-infected with HIV, HCV, or HDV
  9. Patient with metabolic or genetic liver disease that may affect serum ALT level
  10. Habitual alcohol consumption (>140 g/week for male, >70 g/week for female)
  11. Patient not able to stop drugs that may affect ALT or HBV DNA level during study periods (ie. Steroid, immune-suppressants, non-steroidal anti-inflammatory drugs, acetaminophen,)
  12. Pregnant or lactating woman
  13. Menstruating woman unwilling to use appropriate methods of contraception (ie. Condom, oral contraceptives, tubal ligation)
  14. Patient with hepatocellular carcinoma (treated or not treated)
  15. Patient with any untreated malignancy
  16. Patient with history of malignancy cured within 5 years of screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01804387

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Contact: Hyung Joon Yim, M.D 82-31-412-5583

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Korea, Republic of
Korea University Ansan Hospital Recruiting
Ansan, Gyeonggi-do, Korea, Republic of, 425-707
Contact: Hyung Joon Yim, M.D    82-31-412-5583   
Sponsors and Collaborators
Korea University
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Principal Investigator: Hyung Joon Yim, M.D Korea University

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Responsible Party: Hyung Joon Yim, Associate professor, Korea University Identifier: NCT01804387     History of Changes
Other Study ID Numbers: TeSLA study
First Posted: March 5, 2013    Key Record Dates
Last Update Posted: March 5, 2013
Last Verified: March 2013
Keywords provided by Hyung Joon Yim, Korea University:
Chronic Hepatitis B
Lamivudine resistance
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Adefovir dipivoxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents