Ombitasvir/paritaprevir/ritonavir & dasabuvir ± ribavirin following protease inhibitors failure- A prospective multi-centre trial

Liat Deutsch, Inbal Houri, Ziv Ben-Ari, Amir Shlomai, Ella Veitsman, Oranit Cohen-Ezra, Assaf Issachar, Orna Mor, Yael Gozlan, Rafael Bruck, Yoram Menachem, Shira Zelber-Sagi, Helena Katchman, Oren Shibolet

Research output: Contribution to journalArticlepeer-review

Abstract

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/m2). 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).

Original languageEnglish
Article number264
Pages (from-to)264
JournalBMC Infectious Diseases
Volume20
Issue number1
DOIs
StatePublished - 3 Apr 2020

Keywords

  • 2-Naphthylamine
  • AbbVie 3D
  • Anilides/adverse effects
  • Antiviral Agents/adverse effects
  • Carbamates/adverse effects
  • Cyclopropanes
  • Direct acting anti-viral agents
  • Drug Therapy, Combination
  • Female
  • Genotype
  • HCV
  • Hepatitis C/drug therapy
  • Humans
  • Lactams, Macrocyclic
  • Macrocyclic Compounds/adverse effects
  • Male
  • Middle Aged
  • Proline/analogs & derivatives
  • Prospective Studies
  • Protease Inhibitors/adverse effects
  • Protease inhibitors failure
  • Ribavirin/adverse effects
  • Ritonavir/adverse effects
  • Sulfonamides/adverse effects
  • Treatment Outcome
  • Uracil/adverse effects
  • Valine

All Science Journal Classification (ASJC) codes

  • Infectious Diseases

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