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Sponsors and Collaborators: |
Korea University GlaxoSmithKline |
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Information provided by: | Korea University |
ClinicalTrials.gov Identifier: | NCT00531167 |
Antiviral resistance mutations limit the efficacy of therapy for chronic hepatitis B. At year 2, resistance to adefovir may occur as high as 25% in patients with history of lamivudine resistance. Resistance to entecavir is reported to be 10% in lamivudine refractory patients during the same period. However, combination of lamivudine and adefovir decreased the adefovir resistance rate as low as 0% in the recent studies. By overcoming the antiviral resistance, the efficacy of therapy will be maximized. This study is intended to compare the efficacy of two strategies, combination of lamivudine and adefovir vs. entecavir monotherapy in patients with lamivudine resistance.
Condition | Intervention | Phase |
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Chronic Hepatitis B |
Drug: combination of lamivudine+adefovir vs entecavir |
Phase IV |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study |
Official Title: | Prospective Randomized Study for the Comparison of Adding Adefovir Dipivoxil and Switching to Entecavir in Patients With Lamivudine-Resistant Chronic Hepatitis B |
Estimated Enrollment: | 218 |
Study Start Date: | April 2007 |
Estimated Study Completion Date: | December 2010 |
Estimated Primary Completion Date: | December 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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A: Experimental
combination therapy
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Drug: combination of lamivudine+adefovir vs entecavir
Lamivudine 100 mg/day, Adefovir 10 mg/day, Entecavir 0.5 mg/day
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B: Active Comparator
entecavir
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Drug: combination of lamivudine+adefovir vs entecavir
Lamivudine 100 mg/day, Adefovir 10 mg/day, Entecavir 0.5 mg/day
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Recently, published data showed combination of lamivudine and adefovir lead to PCR negativity (<1000 copies/mL) up to 80% in the treatment of lamivudine-resistant chronic hepatitis B at year 2 [Rapti et al. Hepatology 2007 Feb;45(2):307-13.]. Other studies also showed 76% and 69% PCR negativity in mostly HBeAg negative subjects [Lampertico et al. Hepatology 2006 Oct;44(4) Suppl 1:556A-557A, Lampertico et al. Hepatology 2006 Oct;44(4) Suppl 1:693A-694A].
In the study for the treatment of lamivudine-resistant chronic hepatitis B patients which included HBeAg positive subjects more predominantly, entecavir monotherapy showed 34% of PCR negativity (<300 copies/mL) at year 2 [Tenney DJ, et al. Antimicrob Agents Chemother. 2007 Mar;51(3):902-11].
Although it is assumed that combination of lamivudine and adefovir would be more effective than entecavir monotherapy for lamivudine resistant patients, we cannot verify the assumption, because there is no data directly comparing these two strategies until now.
The aim of this study is to determine the most effective therapy for the patients with lamivudine resistant chronic hepatitis B. We will compare the PCR negativity (<60 IU/ml) of HBV DNA at year 2 in patients receiving 'the combination of lamivudine and adefovir' and 'entecavir monotherapy'.
Since we are planning to include lamivudine-resistant chronic hepatitis B patients regardless of HBeAg status, we assumed the PCR negativity (<300 copies/mL or <60 IU/mL) in adefovir-lamivudine combination and entecavir monotherapy group as 55% and 34%, respectively, considering HBeAg status and lower detection limit of PCR.
The result of this study will be able to clearly demonstrate the superiority of combination therapy with lamivudine and adefovir to entecavir monotherapy, which provide us the guide to rescue therapy for patients with lamivudine resistant HBV.
Ages Eligible for Study: | 16 Years to 75 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Any one of following
Contact: Hyung Joon Yim, M.D. | 82-31-412-6565 | gudwns21@medimail.co.kr |
Korea, Republic of, Gyeonggi-do | |
Korea University Ansan Hospital | Recruiting |
Ansan, Gyeonggi-do, Korea, Republic of | |
Contact: Hyung Joon Yim, M.D. +82-31-412-6565 gudwns21@medimail.co.kr | |
Principal Investigator: Hyung Joon Yim, M.D. |
Principal Investigator: | Hyung Joon Yim, M.D. | Korea University |
Responsible Party: | Korea University ( Hyung Joon YIm ) |
Study ID Numbers: | CRT 111098 |
Study First Received: | September 17, 2007 |
Last Updated: | May 19, 2008 |
ClinicalTrials.gov Identifier: | NCT00531167 |
Health Authority: | South Korea: Institutional Review Board |
lamivudine resistant mutations rescue therapy |
Liver Diseases Hepatitis, Chronic Hepatitis, Viral, Human Lamivudine Hepatitis Virus Diseases Digestive System Diseases |
Entecavir Hepatitis B, Chronic Hepatitis B DNA Virus Infections Adefovir dipivoxil Adefovir |
Anti-Infective Agents Anti-HIV Agents Anti-Retroviral Agents Molecular Mechanisms of Pharmacological Action Therapeutic Uses Enzyme Inhibitors |
Antiviral Agents Hepadnaviridae Infections Nucleic Acid Synthesis Inhibitors Pharmacologic Actions Reverse Transcriptase Inhibitors |