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| Name | Class |
|---|---|
| Kyungpook National University Hospital | OTHER |
| Daegu Catholic University Medical Center | OTHER |
| DongGuk University | OTHER |
| Pusan National University Hospital |
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This study will provide a rationale for switch from lamivudine plus adefovir to tenofovir monotherapy in Lamivudine plus Adefovir Treated Lamivudine-resistant chronic hepatitis B patients with Undetectable Hepatitis B Virus DNA
Recently, in Korea, long-term medication of antiviral agents and their resulting resistance expression have been the most serious cause of failure to treat chronic hepatitis B. Exp.
In particular, the annual resistance rate to lamivudine currently widely being used in Korea amounts to about 15 to 20 percents and the rate is expected to reach 70 to 80 percent in four to five years.
The guidelines by the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of the Liver (EASL) recommend a combination therapy with adefovir or tenofovir for patients with lamivudine resistant HBV .
In Korea, however, in case of combined prescription of lamivudine and adefovir, only one of them is covered by the health insurance and therefore many patients are difficult to continue treatment due to their economic conditions.
Tenofovir that has been developed most recently and will be placed on sale sooner or later in Korea has strong antiviral effects, causes little or no emergence of resistant viruses, and is known to have lower nephrotoxicity than adefovir.
In particular, several papers reported that tenofovir has effective and sustaining antiviral effects in patients who had other antiviral agents resistant HBV as well as those who received initial treatment. This shows that patients only with lamivudine resistant HBV can be treated only with tenofovir without a combination therapy and when they have low levels of HBV DNA, treatment is relatively effective despite their resistance to adefovir.
Therefore, it is considered that tenofovir switching therapy in patients with undetectable HBV DNA after lamivudine plus adefovir combination therapy to maintain their virus response.
The results of this study will provide a rationale for switch from lamivudine plus adefovir to tenofovir monotherapy in such patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lamivudine plus adefovir | Active Comparator | Continue lamivudine/adefovir add on treatment (standard treatment) |
|
| Tenofovir | Experimental | Switch from lamivudine/adefovir add on treatment to tenofovir monotherapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lamivudine plus adefovir | Drug | Lamivudine 100mg QD for 96 weeks + Adefovir 10mg QD for 96 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage number of patients with virus reactivation | Percentage number of patients with virus reactivation (HBV DNA > 40 IU/mL on two consecutive samples taken 1 month apart, or persistent HBV DNA levels of 20-40 IU/mL on three consecutive 1 month interval) at Week 96 while on treatment. | Week 96 while on treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Virologic response | Virologic response Percentage number of patients with virus reactivation at Week 48 | Week 96 while on treatment |
| Antiviral resistance | Antiviral resistance percentage number of patients who developed drug resistant mutation at Week 48 and 96 while on randomized therapy. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Byoung Kuk Jang, M.D | Department of Internal Medicine, Keimyung University Dongsan Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Internal Medicine, Keimyung University Dongsan Medical Center | Daegu | ASI|KR|KS002|TAEGU | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29329305 | Derived | Lee HJ, Kim SJ, Kweon YO, Park SY, Heo J, Woo HY, Hwang JS, Chung WJ, Lee CH, Kim BS, Suh JI, Tak WY, Jang BK. Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients. PLoS One. 2018 Jan 12;13(1):e0190581. doi: 10.1371/journal.pone.0190581. eCollection 2018. |
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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 |
|---|---|
| D019259 | Lamivudine |
| C053001 | adefovir |
| C106812 | adefovir dipivoxil |
| D000068698 | Tenofovir |
| ID | Term |
|---|---|
| D016047 | Zalcitabine |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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| OTHER |
| Yeungnam University Hospital | OTHER |
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| Tenofovir | Drug | Tenofovir 300mg QD for 96 weeks |
|
|
| Week 96 while on treatment |
| Biochemical response | Biochemical response percentage number of patients with biochemical breakthrough at Week 48 and 96 | Week 96 while on treatment |
| Serologic response | Serologic response (1) HBeAg loss/seroconversion in HBeAg-positive CHB Percentage number of patients with HBeAg loss or seroconversion at Week 48 and 96. | Week 96 while on treatment |
| Safety assessment | Safety assessment | Week 96 while on treatment |
| 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 |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D000225 | Adenine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |