一项评估索磷布韦联合利巴韦林治疗基因2型慢性丙型肝炎病毒感染受试者的有效性和安全性的单臂、开放、多中心Ⅱ期临床研究  

A phase II,single-arm,open-label,multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection

作　　者：高莹卉[1,19] 李广明 金清龙[3] 赵英仁[4] 贾战生[5] 毛小荣[6] 杨永峰[7] 尚佳[8] 王拱辰[9] 谢雯 巫善明[11] 张明香[12] 侯金林[13] 李东良[14] 南月敏[15] 关玉娟[16] 朱春霞[17] 袁洋洲 魏来 Gao Yinghui;Li Guangming;Jin Qinglong;Zhao Yingren;Jia Zhansheng;Mao Xiaorong;Yang Yongfeng;Shang Jia;Wang Gongchen;Xie Wen;Wu Shanming;Zhang Mingxiang;Hou Jinlin;Li Dongliang;Nan Yuemin;Guan Yujuan;Zhu Chunxia;Yuan Yangzhou;Wei Lai(Department of Hepatology,Peking University People's Hospital,Beijing 100044,China;Center of Liver Disease Study,Beijing Ditan Hospital,Beijing 100015,China;Department of Hepatology,Shanghai Public Health Clinical Center,Shanghai 201508,China;Department of Traditional and Western Medical Hepatology,Shenyang Sixth People's Hospital,Shenyang 110006,China;Department of Infectious Disease,Southern Medical University Southern Hospital,Guangzhou 510515,China;Department of Hepatobiliary,Nanjing Military Region Fuzhou General Hospital,Fuzhou 350025,China;Department of Traditional and Western Medical hepatology,Hebei Medical University Third Hospital,Shijiazhuang 050000,China;Department of Hepatology,Guangzhou Eighth People's Hospital,Guangzhou 510060,China;Nanjing Chia Tai Tianqing Co.,Ltd,Nanjing 210000,China;Department of Hepatology,Peking University People's Hospital,Beijing 100044,China;Peking University International Hospital;Department of Hepatology,Zhengzhou Sixth People's Hospital,Zhengzhou 450061,China;Beijing Tsinghua Changgung Hospital;Department of Hepatobiliary and Pancreatic,Jilin University First Hospital,Changchun 130021,China;Department of Infectious Disease,Xi'an Jiaotong University School of Medicine First Affiliated Hospital,Xi’an 710065,China;Center of Infectious Diseases and Liver Diseases,Fourth Military Medical University Tangdu Hospital,Xi’an 710038,China;Department of Infectious Disease,Lanzhou University First Hospital,Lanzhou 730000,China;Department of Hepatology,Nanjing Second Hospital,Nanjing 210028,China;Department of Infectious Disease,Henan Provincial People's Hospital,Zhengzhou 450003,China;Department of Hepatology,Dalian Sixth People's Hospital,Dalian 116001,China)

机构地区：[1]北京大学人民医院肝病科,100004 [10]北京地坛医院肝病中心,100015 [11]上海市公共卫生临床中心肝病科,201508 [12]沈阳市第六人民医院中西医结合肝病科,110006 [13]南方医科大学南方医院肝病中心暨感染内科,广州510515 [14]南京军区福州总医院肝胆内科,350025 [15]河北医科大学第三医院中西医结合肝病科,石家庄050000 [16]广州市第八人民医院肝病科,510060 [17]南京正大天晴有限公司,210000 [18]北京大学人民医院肝病科(现在北京清华长庚医院),100044 [19]北京大学国际医院 [2]郑州市第六人民医院肝病科,450061 [20]北京清华长庚医院 [3]吉林大学第一医院肝胆胰内科,长春130021 [4]西安交通大学医学院第一附属医院感染性疾病科,710065 [5]第四军医大学唐都医院传染病肝病中心,西安710038 [6]兰州大学第一医院感染科,730000 [7]南京市第二医院肝病科,210028 [8]河南省人民医院感染科,郑州450003 [9]大连市第六人民医院肝病科,116001

出　　处：《中华肝脏病杂志》2019年第5期352-357,共6页Chinese Journal of Hepatology

摘　　要：目的评估索磷布韦(南京正大天晴制药有限公司)联合利巴韦林治疗基因2型慢性丙型肝炎病毒感染的受试者的有效性和安全性。方法在全国16家研究中心筛选初治或经治的基因2型慢性丙型肝炎病毒感染者,所有受试者接受每日一次的索磷布韦(400mg)联合利巴韦林(体质量<75kg,1000mg/d,早上400mg,晚上600mg;体质量≥75kg,1200mg/d,早晚各600mg)治疗12周,停药后随访12周。连续变量采用均值±标准差表示,不同随访时间点病毒学应答的受试者比例及95%置信区间采用极大似然比点估计及Clopper-Pearson区间估计。结果全国16家研究中心共入组132例基因2型慢性丙型肝炎病毒感染的受试者,其中12例受试者伴有肝硬化,其余120例受试者不伴有肝硬化。131例受试者完成了本研究,1例受试者在完成停药后第4周访视后失访。停药12周获得的持续病毒学应答率为96.2%(95%可信区间:92.37%~99.16%)。4例受试者发生病毒学复发。入组的132例受试者中,119例(90.2%)受试者共报告了617例次治疗期不良事件(TEAE),其中与索磷布韦和/或利巴韦林相关TEAE359例次(76.5%)。其中3级及3级以上TEAE9例次,共有6例(4.5%)受试者发生了6例次严重不良事件,仅1例严重不良事件与索磷布韦和利巴韦林相关(不稳定型心绞痛)。无导致停药的不良事件。无导致死亡的不良事件。结论索磷布韦联合利巴韦林治疗基因2型慢性丙型肝炎病毒感染具有较高的SVR率,发生的不良反应大多为轻度,安全性可接受。Objective To evaluate the efficacy and safety of sofosbuvir(Nanjing Zhengda Tianqing Pharmaceutical Co.,Ltd.)combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection.Methods Treatment-na?ve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened.All subjects received once-daily dose of sofosbuvir(400 mg)combined with ribavirin(body weight<75 kg,1 000 mg/day,400 mg in the morning and 600 mg in the evening;body weight>75 kg,1 200 mg/d,600 mg in the morning and 600 mg in the evening)for 12 weeks.Patients were followed-up for a period of 12 weeks after discontinuation of treatment.Continuous variables were expressed as mean±standard deviation.The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval.Results 132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included,12 cases of whom were associated with cirrhosis,and the remaining 120 cases were not associated with cirrhosis.One hundred and thirty-one cases completed the study,and one patient lost to follow-up at week 4 after the end of treatment.The sustained virological response rate was 96.2%(95% confidence interval:92.37%-99.16%)after 12 weeks of drug withdrawal.Virological relapse occurred in four cases.Of the 132 subjects enrolled in the study,119(90.2%)reported 617 adverse events during treatment,of which 359(76.5%)were TEAE related to sofosbuvir and/or ribavirin.There were nine TEAEs of grade 3 and above,and six cases(4.5%)of them had six severe adverse events.Only one serious adverse event was associated with sofosbuvir and ribavirin(unstable angina pectoris).There were no adverse events leading to drug discontinuation or death.Conclusion Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection,and most of the adverse eve

关 键 词：肝炎 丙型 基因2型 直接作用抗病毒药物 索磷布韦 利巴韦林 持续病毒性应答 

分 类 号：R512.63[医药卫生—内科学]