title: Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
abstract: BACKGROUND
  Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection.
  
  
  OBJECTIVE
  To evaluate the safety and efficacy of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) in treatment-naive patients.
  
  
  METHODS
  Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02105467).
  
  
  METHODS
  60 centers in the United States, Europe, Australia, Scandinavia, and Asia.
  
  
  METHODS
  Cirrhotic and noncirrhotic treatment-naive adults with genotype 1, 4, or 6 infection.
  
  
  METHODS
  Oral, once-daily, fixed-dose grazoprevir 100 mg/elbasvir 50 mg for 12 weeks, stratified by fibrosis and genotype. Patients were randomly assigned 3:1 to immediate or deferred therapy.
  
  
  METHODS
  Proportion of patients in the immediate-treatment group achieving unquantifiable HCV RNA 12 weeks after treatment (SVR12); adverse events in both groups.
  
  
  RESULTS
  Among 421 participants, 194 (46%) were women, 157 (37%) were nonwhite, 382 (91%) had genotype 1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299 of 316 (95% [95% CI, 92% to 97%]) achieved SVR12, including 144 of 157 (92% [CI, 86% to 96%]) with genotype 1a, 129 of 131 (99% [CI, 95% to 100%]) with genotype 1b, 18 of 18 (100% [CI, 82% to 100%]) with genotype 4, 8 of 10 (80% [CI, 44% to 98%]) with genotype 6, 68 of 70 (97% [CI, 90% to 100%]) with cirrhosis, and 231 of 246 (94% [CI, 90% to 97%]) without cirrhosis. Virologic failure occurred in 13 patients (4%), including 1 case of breakthrough infection and 12 relapses, and was associated with baseline NS5A polymorphisms and emergent NS3 or NS5A variants or both. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo groups, respectively (difference <0.05 percentage point [CI, -5.4 to 3.1 percentage points]); none were considered drug related. The most common adverse events in the active group were headache (17%), fatigue (16%), and nausea (9%).
  
  
  CONCLUSIONS
  The study lacked an active-comparator control group and included relatively few genotype 4 and 6 infections.
  
  
  CONCLUSIONS
  Grazoprevir-elbasvir achieved high SVR12 rates in treatment-naive cirrhotic and noncirrhotic patients with genotype 1, 4, or 6 infection. This once-daily, all-oral, fixed-combination regimen represents a potent new therapeutic option for chronic HCV infection.
  
  
  BACKGROUND
  Merck & Co.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Reem
authors.initials: R
authors.lastname: Ghalib
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Pockros
authors.forename: Ziv
authors.initials: Z
authors.lastname: Ben Ari
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Brown
authors.forename: Shuyan
authors.initials: S
authors.lastname: Wan
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
authors.forename: Bach-Yen
authors.initials: BY
authors.lastname: Nguyen
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
authors.forename: Janice
authors.initials: J
authors.lastname: Wahl
authors.forename: Eliav
authors.initials: E
authors.lastname: Barr
authors.forename: Joan R
authors.initials: JR
authors.lastname: Butterton
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000577:Amides; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001572:Benzofurans / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005838:Genotype; D006261:Headache / Q000139:chemically induced; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011810:Quinoxalines / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D047029:Lactams, Macrocyclic
chemical_list: D000577:Amides; D000998:Antiviral Agents; D001572:Benzofurans; D002219:Carbamates; D003521:Cyclopropanes; D007093:Imidazoles; D011810:Quinoxalines; D013449:Sulfonamides; C578009:grazoprevir; D047029:Lactams, Macrocyclic; C000589335:elbasvir