Switching to Tenofovir Disoproxil Fumarate vs. Continuing Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response During Entecavir Therapy: STEEP Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Virologic response rate at year 1 (12 months) (HBV DNA < 20 IU/mL)
研究概览
简要总结
Entecavir, a potent antiviral agent, has been widely used for treatment-naïve chronic hepatitis B patients. However, about 20% of patients showed partial virologic response after 2 year of entecavir therapy (33% in HBeAg positive, 10% in HBeAg negative patients). Tenofovir is a nucleotide analogue with more potent antiviral activity. In addition, there is no cross resistance between the two drugs. Therefore it is assumed that tenofovir would be effective in the treatment of chronic hepatitis B patients who shows partial virologic response (detectable HBV DNA by real time PCR after 12 months of treatment) despite treatment with entecavir. In this study, we will compare the efficacy of switching to tenofovir with continuing entecavir in patients who shows partial virologic response to entecavir.
详细描述
The number of patients needed was calculated using PASS 2008. We hypothesized that two-thirds (65%) of the patients receiving TDF, and one-fifth (20%) of the patients receiving ETV, would achieve virologic response. We also assumed a 15% drop-out rate; thus, 22 patients were needed in each group to achieve 80% power to demonstrate a difference between the groups with a 5% level of significance.
The primary efficacy end point will be analyzed on a per-protocol basis, including only those patients who had completed the treatment schedule of study. In contrast, the intention-to-treat analysis will include all randomized subjects, even those dropped-out from the study before 12 months, as cases of treatment failure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CHB patients (positive HBsAg more than 6 months)
- •Age 19 years old
- •HBeAg positive or negative patients
- •Patients receiving entecavir 0.5 mg more than 12 months
- •Detectable HBV DNA by real time PCR (HBV > 60 IU/mL)
- •Compensated liver function (Child-Pugh-Turcotte score ≤7, prothrombin time 3 sec above ULN or INR ≤1.5, serum albumin >3 g/dL, total bilirubin <2.5 mg/dL, no history of variceal bleeding, diuretics or ascites requiring paracentesis, hepatic encephalopathy)
排除标准
- •History of treatment with nucleotide analogue other than 0.5 mg of ETV
- •Serum creatinine level > 1.5 mg/dL or creatinine clearance < 50 mL/min
- •Absolute neutrophil count ≤ 1000 cell/mL
- •Hemoglobin level ≤ 10 g/dL in men or ≤ 9 g/dL in women
- •Antiviral resistance mutations on rtT184, rtS202, or rtM250 + rtM204V/I
- •A positive antibody test for human immunodeficiency virus, hepatitis C virus, or hepatitis D virus
- •Pregnancy or lactation
- •HCC (in cases where alfa-fetoprotein levels were over 100 ng/mL, abdominal computed tomography or magnetic resonance image was performed to exclude HCC)
- •Untreated malignancy other than HCC.
研究组 & 干预措施
entecavir
standard drugs
干预措施: entecavir (Drug)
tenofovir
study drugs
干预措施: tenofovir (Drug)
结局指标
主要结局
Virologic response rate at year 1 (12 months) (HBV DNA < 20 IU/mL)
时间窗: up to the end of year 1 (12 months)
次要结局
- -Degree of HBV DNA reduction, mean HBV DNA, biochemical and serologic response rates, resistance, and adverse events at year 1(up to the end of year 1 (12 months))
研究者
Hyung Joon Yim
Associate professor
Korea University