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Journal Article Multicenter Study Randomized Controlled Trial Equivalence Trial Ppublish 1 citation

PubMed: 42815507 DOI: 10.1016/S0140-6736(26)01380-2

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.

Lancet 408(10564):1593-1602

Authors: Amit Goel, Sumit Rungta, Vinod Kumar, Shalimar, Ajay Kumar, Harshita Katiyar, Surender Singh, Amar Deep, Ajay Kumar Mishra, Ashish Awasthi, Vikasendu Agarwal, Anurag Kumar Tiwari, Dawesh Prakash Yadav, Sunit Kumar Shukla, Ujjwal Sonika, Radha Krishan Dhiman, Bharat Bhushan Rewari, Rakesh Aggarwal

Affiliations

  • Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
  • Department of Gastroenterology, King George's Medical University, Lucknow, India.
  • Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
  • Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
  • Department of Gastroenterology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India.
  • CSIR-Central Drug Research Institute, Lucknow, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
  • Directorate of Medical and Health Services, Uttar Pradesh, Lucknow, India.
  • WHO Regional Office for South East Asia, New Delhi, India.
  • Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Abstract

BACKGROUND

Chronic hepatitis C virus (HCV) infection without cirrhosis can be treated with 12 weeks of sofosbuvir-velpatasvir combination therapy. 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.

METHODS

RESOLVE was a multicentre, open-label, non-inferiority, randomised controlled trial, conducted in five publicly funded hospitals in India. 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. 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. The trial was registered with the Clinical Trial Registry of India, CTRI/2022/03/041368, and is complete.

FINDINGS

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. 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). Further, on intention-to-treat analysis, 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). No participant had any drug-related serious adverse event or drug discontinuation due to an adverse event.

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

FUNDING

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

MeSH

Hepatitis C, Chronic, Hepatitis C, Pharmaceutical Preparations, Hepatitis, Chronic, Drug-Related Side Effects And Adverse Reactions, Sofosbuvir, Therapeutics, Infections, Hepatitis