title: Treatment With Ledipasvir-Sofosbuvir for 12 or 24 Weeks in Kidney Transplant Recipients With Chronic Hepatitis C Virus Genotype 1 or 4 Infection: A Randomized Trial.
abstract: BACKGROUND
  Use of interferon and ribavirin to treat chronic hepatitis C virus (HCV) infection in kidney transplant recipients is limited because of the risk for allograft rejection and poor tolerability.
  
  
  OBJECTIVE
  To evaluate the safety and efficacy of the interferon- and ribavirin-free regimen ledipasvir-sofosbuvir in kidney transplant recipients with chronic genotype 1 or 4 HCV infection.
  
  
  METHODS
  Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT02251717).
  
  
  METHODS
  5 sites in Europe.
  
  
  METHODS
  Treatment-naive or -experienced kidney transplant recipients with chronic genotype 1 or 4 HCV infection, with or without compensated cirrhosis, and with an estimated glomerular filtration rate (eGFR) of 40 mL/min or greater were randomly assigned 1:1 to receive ledipasvir (90 mg) and sofosbuvir (400 mg) for 12 or 24 weeks.
  
  
  METHODS
  The primary end point was sustained virologic response at 12 weeks after therapy ended (SVR12).
  
  
  RESULTS
  Among 114 patients, the median age was 53 years, 58% were male, 91% had genotype 1 infection, 69% were treatment naive, and 15% had compensated cirrhosis. The median eGFR was 56 mL/min (range, 35 to 135 mL/min). One hundred percent of patients (57 of 57) treated for 12 weeks (95% CI, 94% to 100%) and 100% of those (57 of 57) treated for 24 weeks (CI, 94% to 100%) achieved SVR12. Serious adverse events were reported in 13 patients (11%). Of these, 3 events-syncope, pulmonary embolism, and serum creatinine increase-in 3 patients were determined to be treatment related. One patient permanently discontinued treatment because of an adverse event (syncope). The most frequent adverse events overall were headache (n = 22 [19%]), asthenia (n = 16 [14%]), and fatigue (n = 11 [10%]).
  
  
  CONCLUSIONS
  The study was open label, no inferential statistics were planned, and only patients with genotype 1 or 4 infection were included. Few patients with HCV genotype 1a and cirrhosis were enrolled.
  
  
  CONCLUSIONS
  Treatment with ledipasvir-sofosbuvir for 12 or 24 weeks was well-tolerated and seemed to have an acceptable safety profile among kidney transplant recipients with HCV genotype 1 or 4 infection, all of whom achieved SVR12.
  
  
  BACKGROUND
  Gilead Sciences.
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: Alessio
authors.initials: A
authors.lastname: Aghemo
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: Hadas
authors.initials: H
authors.lastname: Dvory-Sobol
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Hyland
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: Chohee
authors.initials: C
authors.lastname: Yun
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Massetto
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Bourlière
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Peck-Radosavljevic
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Manns
authors.affiliation: From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use*; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; D007166:Immunosuppressive Agents; C586541:ledipasvir; D000069474:Sofosbuvir