Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial
Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial
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DOI：
10.1016/s0140-6736(10)60934-8
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发表时间：
2010-08-01
期刊：
影响因子：
168.9
通讯作者：
Albrecht, Janice K.
中科院分区：
文献类型：
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作者：
Kwo, Paul Y.;Lawitz, Eric J.;Albrecht, Janice K.
背景 聚乙二醇干扰素联合利巴韦林治疗 48 周后，只有不到一半的基因 1 型慢性丙型肝炎病毒感染患者实现了持续病毒学应答 (SVR)。我们测试了博普瑞韦（一种 NS3 丙型肝炎病毒口服蛋白酶抑制剂）与聚乙二醇干扰素 alfa-2b 和利巴韦林联合治疗的疗效。 方法 在本试验的第 1 部分中，在美国、Qmada 和欧洲的 67 个地点进行，520 名基因 1 型丙型肝炎病毒感染的初治患者被随机分配接受聚乙二醇干扰素 alfa-2b 1.5 μg/kg 加利巴韦林治疗每天 800-1400 mg，持续 48 周（PR48；n=104）；每天使用聚乙二醇干扰素 alfa-2b 和利巴韦林，持续 4 周，然后使用聚乙二醇干扰素 alfa-2b、利巴韦林和博普瑞韦 800 mg，每天 3 次，持续 24 周 (PR4/PR824；11=103) 或 44 周 (PR4/PRB44；n=103)，或聚乙二醇干扰素 alfa-2b、利巴韦林和博普瑞韦波普瑞韦每天 3 次，持续 28 周（PRB28；n=107）或 43 周（PRB48；n=103）。在第 2,75 名患者中，被随机分配接受 PRB48 (n=16) 或低剂量利巴韦林 (400-1000 mg) 加聚乙二醇干扰素 alfa-2b 和博普瑞韦，每天 3 次，持续 48 周（低剂量 PRB48；n=59）。主要终点是治疗后 24 周的 SVR。分析是按意向治疗进行的。这项研究已在 ClinicalTrials.gov 注册，编号为 NCT00423670。 结果 所有四个波普瑞韦组的患者的 SVR 率均高于对照组（PRB28 为 58/107 [54%, 95% CI 44-64]，p=0.013；PRB28 为 58/103 [56%, 44-66]，p=0.005） PR4/PR824；69/103 [67%，57-761，p
Background Peginterferon plus ribavirin achieves sustained virological response (SVR) in fewer than half of patients with genotype 1 chronic hepatitis C virus infection treated for 48 weeks. We tested the efficacy of boceprevir, an NS3 hepatitis C virus oral protease inhibitor, when added to peginterferon alfa-2b and ribavirin.Methods In part 1 of this trial, undertaken in 67 sites in the USA, Qmada, and Europe, 520 treatment-naive patients with genotype 1 hepatitis C virus infection were randomly assigned to receive peginterferon alfa-2b 1.5 mu g/kg plus ribavirin 800-1400 mg daily for 48 weeks (PR48; n=104); pegmterferon alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir 800 mg three times a day for 24 weeks (PR4/PR824; 11=103) or 44 weeks (PR4/PRB44; n=103), or peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 28 weeks (PRB28; n=107) or 43 weeks (PRB48; n=103). In part 2,75 patients were randomly assigned to receive either PRB48 (n=16) or low-dose ribavirin (400-1000 mg) plus peginterferon alfa-2b and boceprevir three times a day for 48 weeks (low-dose PRB48; n=59) Randomisation was by computer-generated code, and study personnel and patients were not masked to group assignment. The primary endpoint was SVR 24 weeks after treatment. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00423670.Findings Patients in all four boceprevir groups had higher rates of SVR than did the control group (58/107 [54%, 95% CI 44-64], p=0.013 for PRB28; 58/103 [56%, 44-66], p=0.005 for PR4/PR824; 69/103 [67%, 57-761, p