恩替卡韦治疗拉米夫定失效的慢性乙型肝炎患者多中心随机双盲对照临床研究

A double-blinded, randomized, placebo-controlled trial of entecavir for Chinese hepatitis B patients failed with lamivudine therapy

目的 研究恩替卡韦对拉米夫定治疗失效的慢性乙型肝炎 (CHB)患者的疗效和安全性。方法 采用多中心、随机、双盲、安慰剂对照的临床试验 ,选择拉米夫定治疗失效的CHB病人 14 5例 ,按 4∶1比例随机分为恩替卡韦组 116例 ,安慰剂组 2 9例。完成为期 12周的治疗后 ,检测血清HBVDNA水平、HBeAg和肝生化功能的变化。结果 恩替卡韦组在开始治疗后即有显著的抗病毒效果 ,直至治疗结束。用聚合酶链反应 (PCR ,AmplicorCobas)定量法检测病人HBVDNA的平均下降幅度 ,恩替卡韦和安慰剂组分别为 :4.3 0对数值 (log1 0 )和 0 .15对数值 (log1 0 ) ,P值均 <0 .0 0 0 1;在 12周时 ,用bDNA方法检测 ,两组病人HBVDNA转阴率 (<0 .7mEq ml)为 74%和 10 %。丙氨酸氨基转移酶 (ALT)的复常率为 71%和 7%。两组不良事件的发生率相当 (3 3 %对 2 8% )。无 1例发生药物相关的严重不良反应。结论 用恩替卡韦治疗拉米夫定失效的病人 12周 ,1.0mg d剂量在降低HBVDNA水平和ALT复常方面明显优于安慰剂 。

Objective To evaluate the efficacy and safety of entecavir (ETV) for patients with lamivudine refractory.Methods This was a multicenter, double-blinded, randomized (4:1) and placebo-controlled trial comparing the safety and efficacy of ETV (1.0mg once daily) with placebo administered for 12 weeks to patients with lamivudine refractory. During the 12-week double-blinded dosing phase, HBV DNA levels were measured by quantitative PCR and bDNA assay. Liver function tests, HBV serology and safety assessments were also conducted.Results The mean reduction from baseline in HBV DNA by PCR assay at week 12 was significantly greater in the ETV group compared with placebo ((4.3) log_(10) vs (0.15) log_(10), P<(0.0001)). The superior of ETV (1.0) mg was demonstrated by proportion of patients with HBV DNA by bDNA assay ≥(0.7) mEq/ml at baseline who achieved HBV DNA <(0.7) mEq/ml (undetected level) at week 12 (74%vs 10%, P<(0.0001)). Among patients with abnormal ALT values at baseline, a significant higher percentage of patients in the ETV group had achieved ALT normalization at week 12 than in the placebo group (71% vs 7%, P<(0.0001)). The overall incidence of adverse events was similar between ETV and placebo groups (33% vs 28%). There is no severe adverse event related to the study medications in the trial.Conclusion At week 12, ETV was statistically superior to placebo in the magnitude of reduction of HBV DNA and in the proportion of patients with normalization of ALT. It is anticipated that longer duration of therapy will result in significant clinical benefit.