Chronic Hepatitis B
Conditions
Keywords
adefovir, lamivudine, entecavir resistance
Brief summary
* Entecavir has been one of the option for treatment of lamivudine resistant chronic hepatitis B (CHB). * In case of entecavir resistance, adefovir could be used. However, sequential monotherapy may result in multidrug resistance. * It is thought that adefovir and lamivudine combination therapy reduce the risk of adefovir resistance, thereby continued therapy will lead to suppression of hepatitis B virus (HBV) DNA to be undetectable in patients with entecavir resistance. * This study aim to evaluate the efficacy of adefovir and lamivudine combination therapy in CHB patients with entecavir resistance.
Detailed description
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.
Interventions
DRUGADEFOVIR, LAMIVUDINE
Adefovir/10mg tablet/once a day/52week Lamivudine/100mg tablet/once a day/52week
Sponsors
GlaxoSmithKline
Korea University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Chronic hepatitis B patients (positive HBsAg \> 6 months) 2. Age \> 18 year old 3. History of treatment with entecavir more than 6 months 4. Proven entecavir resistant mutation (rtT184S/A/I/L/G/C/M, rtS202G/C/I, or rtM250I/V) 5. HBV DNA level\> 2000 IU/mL 6. Compensated liver disease (Child-Pugh-Turcotte score over 7; prothrombin time prolonged more than 3 sec above ULN or INR over 1.5; serum albumin \>3 g/dL; total bilirubin \<2.5 mg/dL; No history of variceal bleeding, ascites, or hepatic encephalopathy) 7. Patients willing to give informed consent
Exclusion criteria
1. Out of inclusion criteria 2. Any one of following * Serum phosphorus level under 2.4 mg/dL * Serum creatinine level over 1.5 mg/dL or creatinine clearance \<50 mL/min * Absolute neutrophil count lower than 1000 cell/mL * Hb level under 10 g/dL (male), under 9 g/dL (female) * Serum AFP \>100 ng/mL 3. History of treatment with interferon-alfa, thymosin-alfa 1, or nucleos(t)ide analogue other than entecavir in 6 months of screening 4. History of adefovir resistance (detection of rtA181T/Vor rtN236T at screening or in the past) 5. Recipient of organ transplantation 6. Positive antibody test to HIV, HCV or HDV 7. Pregnant or breast feeding women 8. Patients with hepatocellular carcinoma or uncontrolled malignant disease 9. Habitual alcohol drinker (\>140 g/week for men, \>70 g/week for women) -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Degree of HBV DNA reduction from baseline | at week 52 | Degree of HBV DNA reduction from baseline during 52 week-period of adefovir and lamivudine combination therapy will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ALT normalization | at week 52 | — |
| HBeAg loss | at week 52 | — |
| HBV DNA undetectability by PCR (<60 IU/mL) | at week 52 | — |
| Development of adefovir resistance | at week 52 | — |
| Virologic breakthrough | at week 52 | virologic breakthrough is defined by increase of HBV DNA above 10 times the lowest level (na dir). |
| HBeAg to anti- HBe seroconversion | at week 52 | — |
Countries
South Korea
Outcome results
None listed