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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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Entecavir is a potent antiviral agent for the treatment of chronic hepatitis B (CHB). However, the incidence of entecavir resistance increases over 50% at 5th year in lamivudine-refractory CHB patients. Considering cross resistance profile, adefovir is a good option for managing entecavir resistance. However adefovir monotherapy may lead to adefovir resistance, because entecavir resistant hepatitis B virus (HBV) retain lamivudine resistance. Previously, combination of adefovir and lamivudine was reported to be effective in a patient with entecavir resistance, but only as a case report form. No further data are available on this combination therapy in a sufficient number of patients. It is thought that adefovir and lamivudine combination therapy reduce the risk of adefovir resistance, thereby continued combination treatment will result in suppression of HBV DNA to be undetectable in patients with entecavir resistance.
The aim of this study is to evaluate the efficacy of adefovir and lamivudine combination therapy in CHB patients with entecavir resistance.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adefovir and lamivudine combination | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ADEFOVIR, LAMIVUDINE | Drug | Adefovir/10mg tablet/once a day/52week Lamivudine/100mg tablet/once a day/52week |
|
| Measure | Description | Time Frame |
|---|---|---|
| Degree of HBV DNA reduction from baseline | Degree of HBV DNA reduction from baseline during 52 week-period of adefovir and lamivudine combination therapy will be assessed. | at week 52 |
| Measure | Description | Time Frame |
|---|---|---|
| HBV DNA undetectability by PCR (<60 IU/mL) | at week 52 | |
| ALT normalization | at week 52 | |
| HBeAg loss |
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Inclusion Criteria:
Exclusion Criteria:
Out of inclusion criteria
Any one of following
History of treatment with interferon-alfa, thymosin-alfa 1, or nucleos(t)ide analogue other than entecavir in 6 months of screening
History of adefovir resistance (detection of rtA181T/Vor rtN236T at screening or in the past)
Recipient of organ transplantation
Positive antibody test to HIV, HCV or HDV
Pregnant or breast feeding women
Patients with hepatocellular carcinoma or uncontrolled malignant disease
Habitual alcohol drinker (>140 g/week for men, >70 g/week for women) -
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| Name | Affiliation | Role |
|---|---|---|
| HYUNG JOON YIM, M.D., Ph.D. | Korea University Ansan Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chungbuk National University Hospital | Cheongju-si | Chngcheongbuk-do | South Korea | |||
| Yonsei University Wonju Christian Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9392700 | Background | Lee WM. Hepatitis B virus infection. N Engl J Med. 1997 Dec 11;337(24):1733-45. doi: 10.1056/NEJM199712113372406. No abstract available. | |
| 19714720 | Background | Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009 Sep;50(3):661-2. doi: 10.1002/hep.23190. No abstract available. |
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| ID | Term |
|---|---|
| D019694 | Hepatitis B, Chronic |
| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C053001 | adefovir |
| D019259 | Lamivudine |
| ID | Term |
|---|---|
| D016047 | Zalcitabine |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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| at week 52 |
| HBeAg to anti- HBe seroconversion | at week 52 |
| Development of adefovir resistance | at week 52 |
| Virologic breakthrough | virologic breakthrough is defined by increase of HBV DNA above 10 times the lowest level (na dir). | at week 52 |
| Wŏnju |
| Gangwon-do |
| South Korea |
| Korea University Ansan Hospital | Ansan | Gyeonggi-do | South Korea |
| Hallym University, Sacred Heart Hospital | Anyang-si | Gyeonggi-do | South Korea |
| The Catholic University of Korea, Euijeongbu Saint Mary's Hospital | Euijeongbu | Gyeonggi-do | South Korea |
| Gachon University Gil Medical Center | Incheon | South Korea |
| Inha University Hospital | Incheon | South Korea |
| Hallym University, Gangnam Sacred Heart Hospital | Seoul | South Korea |
| Korea University Anam Hospital | Seoul | South Korea |
| 19280622 | Background | Tenney DJ, Rose RE, Baldick CJ, Pokornowski KA, Eggers BJ, Fang J, Wichroski MJ, Xu D, Yang J, Wilber RB, Colonno RJ. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy. Hepatology. 2009 May;49(5):1503-14. doi: 10.1002/hep.22841. |
| 16941700 | Background | Yim HJ, Hussain M, Liu Y, Wong SN, Fung SK, Lok AS. Evolution of multi-drug resistant hepatitis B virus during sequential therapy. Hepatology. 2006 Sep;44(3):703-12. doi: 10.1002/hep.21290. |
| 17983801 | Background | Lampertico P, Vigano M, Manenti E, Iavarone M, Sablon E, Colombo M. Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine-resistant hepatitis B patients. Gastroenterology. 2007 Nov;133(5):1445-51. doi: 10.1053/j.gastro.2007.08.079. Epub 2007 Sep 2. |
| 17256746 | Background | Rapti I, Dimou E, Mitsoula P, Hadziyannis SJ. Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B. Hepatology. 2007 Feb;45(2):307-13. doi: 10.1002/hep.21534. |
| 17239478 | Result | Villet S, Ollivet A, Pichoud C, Barraud L, Villeneuve JP, Trepo C, Zoulim F. Stepwise process for the development of entecavir resistance in a chronic hepatitis B virus infected patient. J Hepatol. 2007 Mar;46(3):531-8. doi: 10.1016/j.jhep.2006.11.016. Epub 2006 Dec 18. |
| 17935165 | Result | Yatsuji H, Hiraga N, Mori N, Hatakeyama T, Tsuge M, Imamura M, Takahashi S, Fujimoto Y, Ochi H, Abe H, Maekawa T, Suzuki F, Kumada H, Chayama K. Successful treatment of an entecavir-resistant hepatitis B virus variant. J Med Virol. 2007 Dec;79(12):1811-7. doi: 10.1002/jmv.20981. |
| D018347 |
| Hepadnaviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011743 |
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D015224 | Dideoxynucleosides |