在蛋白酶抑制剂失败后使用奥比他韦/帕利瑞韦/利托那韦和达沙布韦±利巴韦林 - 一项前瞻性多中心试验。
Ombitasvir/paritaprevir/ritonavir & dasabuvir ± ribavirin following protease inhibitors failure - a prospective multi-centre trial.
机构信息
Department of Gastroenterology and Liver diseases, Tel Aviv Sourasky Medical Centre and Tel-Aviv University, 6 Weizmann St, 64239, Tel-Aviv, Israel.
Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
出版信息
BMC Infect Dis. 2020 Apr 3;20(1):264. doi: 10.1186/s12879-020-4921-3.
BACKGROUND
Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease and hepatocellular carcinoma. Treatment with first generation protease inhibitors (PI) + peg-interferon (pegIFN) and ribavirin (RBV) achieved sustained virologic response (SVR) rates of 65-75% but was associated with multiple side effects. The aim of this study was to evaluate safety and efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir (3D) ± RBV in HCV genotype 1 patients that failed previous treatment with first generation PIs.
METHODS
An investigator-initiated, open-label, multi-centre clinical trial. HCV Genotype 1 patients who were previously null/partial responders or relapsers to telaprevir, boceprevir or simepravir+pegIFN/RBV and met eligibility criteria were included. 3D ± RBV were administrated for 12 or 24 weeks according to label. The primary outcome was antiviral response (SVR12); Secondary outcomes were patient reported outcomes, adverse events and resistance associated variants.
RESULTS
Thirty-nine patients initiated treatment according to study protocol (59% men, age 54.0 ± 8.7 years, BMI 28.7 ± 4.5 kg/m). Thirty-seven (94.9%) completed the study. Thirty-five patients had genotype 1b (9 cirrhotics) and 4 had genotype 1a (2 cirrhotics). Intention-to-treat SVR12 was 92.3% and per-protocol SVR12 was 97.3%. The rate of advanced fibrosis (FibroScan® score F3-4) declined from 46.2 to 25.7% (P = 0.045). Abnormal ALT levels declined from 84.6 to 8.6% (P < 0.001). Seven patients (17.9%) experienced serious adverse events (3 Psychiatric admissions, 1 pneumonia, 1 ankle fracture, 2 palpitations), and 12 patients (30.8%) experienced self-reported adverse events, mostly weakness.
CONCLUSION
3D ± RBV is safe and effective in achieving SVR among patients with HCV genotype 1 who failed previous first-generation PI treatment.
TRIAL REGISTRATION
NCT02646111 (submitted to ClinicalTrials.gov, December 28, 2015).
背景
丙型肝炎病毒（HCV）感染是慢性肝病和肝细胞癌的主要原因。第一代蛋白酶抑制剂（PI）+聚乙二醇干扰素（pegIFN）和利巴韦林（RBV）的治疗可实现持续病毒学应答（SVR）率为 65-75%，但与多种副作用相关。本研究的目的是评估 Ombitasvir/Paritaprevir/Ritonavir 和 Dasabuvir（3D）±RBV 在先前第一代 PI 治疗失败的 HCV 基因型 1 患者中的安全性和疗效。
方法
这是一项由研究者发起的、开放标签、多中心临床试验。纳入了先前对特拉泼维、博赛泼维或西美瑞韦+pegIFN/RBV 治疗无应答/部分应答或复发且符合入选标准的 HCV 基因型 1 患者。根据标签，3D±RBV 治疗 12 或 24 周。主要结局是抗病毒应答（SVR12）；次要结局是患者报告结局、不良事件和耐药相关变异。
结果
根据研究方案，39 例患者开始治疗（59%为男性，年龄 54.0±8.7 岁，BMI 28.7±4.5kg/m2）。37 例（94.9%）完成了研究。35 例患者为基因型 1b（9 例为肝硬化），4 例为基因型 1a（2 例为肝硬化）。意向治疗 SVR12 为 92.3%，符合方案的 SVR12 为 97.3%。晚期纤维化（FibroScan®评分 F3-4）的发生率从 46.2%下降至 25.7%（P=0.045）。异常 ALT 水平从 84.6%下降至 8.6%（P<0.001）。7 例患者（17.9%）发生严重不良事件（3 例精神科住院，1 例肺炎，1 例踝部骨折，2 例心悸），12 例患者（30.8%）发生自报告不良事件，主要为虚弱。
结论
在先前第一代 PI 治疗失败的 HCV 基因型 1 患者中，3D±RBV 可安全有效地实现 SVR。
试验注册
NCT02646111（于 2015 年 12 月 28 日提交至 ClinicalTrials.gov）。
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