8 weeks versus 12 weeks of sofosbuvir-velpatasvir for treatment-naive, non-cirrhotic, chronic hepatitis C (RESOLVE): a multicentre, open-label, non-inferiority, randomised controlled trial in India.

We aimed to assess whether a shorter 8-week treatment regimen of this combination was non-inferior to the standard 12-week regimen in successfully clearing HCV infection in HCV-infected patients without evidence of cirrhosis.

我们旨在评估这种联合疗法的8周治疗方案是否与标准的12周治疗方案在清除HCV感染方面具有非劣效性，针对的是无肝硬化证据的HCV感染者。

Methods

RESOLVE was a multicentre, open-label, non-inferiority, randomised controlled trial, conducted in five publicly funded hospitals in India.

RESOLVE是一项多中心、开放标签、非劣效性、随机对照试验，于印度的五家公立资助医院进行。

We randomly assigned (1:1) treatment-naive adults (aged ≥18 years) with non-cirrhotic HCV mono-infection to receive sofosbuvir 400 mg and velpatasvir 100 mg (orally, daily) for either 8 weeks or 12 weeks.

我们随机分配（1:1）治疗未经验的成人（≥18岁）HCV单感染且无肝硬化患者，接受索非布韦400毫克和维帕他韦100毫克（口服，每日一次）治疗，为期8周或12周。

The primary outcome was the proportion of participants with sustained virological response-ie, absence of quantifiable HCV RNA at 12 weeks after treatment completion (SVR12), with 95% assumed proportion with 12-week treatment, 5% non-inferiority margin, 2·5% one-sided alpha error, and 90% study power in the per-protocol population.

主要结果是持续病毒学应答的比例，即治疗完成12周后无定量HCV RNA（SVR12），假设12周治疗的比例为95%，非劣效性边界为5%，单侧α错误为2·5%，意向性治疗人群中的研究功效为90%。

The trial was registered with the Clinical Trial Registry of India, CTRI/2022/03/041368, and is complete.

该试验已在印度临床试验注册处注册，注册号为CTRI/2022/03/041368，且已完成。

Results

Between May 15, 2022, and Sept 10, 2024, we screened 1620 participants, of whom 880 (54·3%) were enrolled in the study and randomly assigned to the 12-week (n=437 [50%]) or 8-week (n=443 [50%]) groups. 455 (52%) participants were women, 425 (48%) were men, and the median age was 35 years (IQR 28 to 47). 816 (93%) participants completed the intended 12-week (401 [92%] of 437) or 8-week (415 [94%] of 443) treatment and SVR12 testing.

在2022年5月15日至2024年9月10日期间，我们筛查了1620名参与者，其中880名（54·3%）被纳入研究并随机分配到12周组（n=437 [50%]）或8周组（n=443 [50%]）。455名（52%）参与者为女性，425名（48%）为男性，中位年龄为35岁（四分位数间距28至47）。816名（93%）参与者完成了预期的12周（401名[92%]中的437名）或8周（415名[94%]中的443名）治疗和SVR12检测。

On per-protocol analysis, the proportion reaching SVR12 with 8-week treatment (410/415; 98·8% [95% CI 97·2 to 99·6]) was non-inferior to 12-week treatment (397/401; 99·0% [97·5 to 99·7]), with a risk difference of 0·2% (-1·5 to 1·9).

在按方案分析中，接受8周治疗达到SVR12的比例（410/415; 98·8% [95% CI 97·2 to 99·6]）与接受12周治疗（397/401; 99·0% [97·5 to 99·7]）相当，风险差异为0·2%（-1·5至1·9）。

Further, on intention-to-treatanalysis, the proportion of participants reaching SVR12 with 8-week treatment (414/443; 93·5% [90·9 to 95·5]) was non-inferior to 12-week treatment (401/437; 91·8% [88·8 to 94·2]) with a risk difference of -1·7% (-5·2 to 1·9).

进一步的意向性治疗分析显示，接受8周治疗的参与者中达到SVR12的比例（414/443；93.5% [90.9至95.5]）与接受12周治疗的（401/437；91.8% [88.8至94.2]）相当，风险差异为-1.7%（-5.2至1.9）。

No participant had any drug-related serious adverse eventor drug discontinuation due to an adverse event.

没有参与者出现任何与药物相关的严重不良事件或因不良事件而停药。

interpretation

An 8-week regimen of sofosbuvir-velpatasvir was similar in efficacy to the standard 12-week treatment in individuals with chronic HCV infection without cirrhosis.

在没有肝硬化的慢性HCV感染个体中，8周的索非布韦-维帕他韦方案在疗效上与标准的12周治疗相似。

This finding supports shortening the duration of treatment in such patients.

这一发现支持在这些患者中缩短治疗时间。

funding

Indian Council of Medical Research, Department of Health Research, Government of India.

印度医学研究委员会，卫生研究部，印度政府。