Efficacy of Adefovir and Lamivudine Combination Therapy in Patients With Entecavir Resistance
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 9
- 主要终点
- Degree of HBV DNA reduction from baseline
研究概览
简要总结
- 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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic hepatitis B patients (positive HBsAg > 6 months)
- •Age > 18 year old
- •History of treatment with entecavir more than 6 months
- •Proven entecavir resistant mutation (rtT184S/A/I/L/G/C/M, rtS202G/C/I, or rtM250I/V)
- •HBV DNA level> 2000 IU/mL
- •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)
- •Patients willing to give informed consent
排除标准
- •Out of inclusion criteria
- •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
- •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) -
研究组 & 干预措施
Adefovir and lamivudine combination
干预措施: ADEFOVIR, LAMIVUDINE (Drug)
结局指标
主要结局
Degree of HBV DNA reduction from baseline
时间窗: at week 52
Degree of HBV DNA reduction from baseline during 52 week-period of adefovir and lamivudine combination therapy will be assessed.
次要结局
- HBV DNA undetectability by PCR (<60 IU/mL)(at week 52)
- ALT normalization(at week 52)
- HBeAg loss(at week 52)
- HBeAg to anti- HBe seroconversion(at week 52)
- Development of adefovir resistance(at week 52)
- Virologic breakthrough(at week 52)
研究者
Hyung Joon Yim
Associate Professor
Korea University