PMID- 26976799
OWN - NLM
STAT- MEDLINE
DCOM- 20170522
LR  - 20220331
IS  - 1528-0012 (Electronic)
IS  - 0016-5085 (Linking)
VI  - 150
IP  - 7
DP  - 2016 Jun
TI  - Efficacy of Direct-Acting Antiviral Combination for Patients With Hepatitis C 
      Virus Genotype 1 Infection and Severe Renal Impairment or End-Stage Renal 
      Disease.
PG  - 1590-1598
LID - S0016-5085(16)00326-7 [pii]
LID - 10.1053/j.gastro.2016.02.078 [doi]
AB  - BACKGROUND & AIMS: Although hepatitis C virus (HCV) infection is common in 
      patients with end-stage renal disease, highly efficacious, well-tolerated, 
      direct-acting antiviral regimens have not been extensively studied in this 
      population. We investigated the safety and efficacy of ombitasvir co-formulated 
      with paritaprevir and ritonavir, administered with dasabuvir (with or without 
      ribavirin) in a prospective study of patients with stage 4 or 5 chronic kidney 
      disease (CKD). METHODS: We performed a single-arm, multicenter study of 
      treatment-naive adults with HCV genotype 1 infection, without cirrhosis and with 
      CKD stage 4 (estimated glomerular filtration rate, 15-30 mL/min/1.73 m(2)) or 
      stage 5 (estimated glomerular filtration rate, <15 mL/min/1.73 m(2) or requiring 
      hemodialysis). Twenty patients were given ombitasvir co-formulated with 
      paritaprevir and ritonavir, administered with dasabuvir for 12 weeks. Patients 
      with HCV genotype 1a infections also received ribavirin (n = 13), whereas those 
      with genotype 1b infection did not (n = 7). The primary end point was sustained 
      virologic response (serum HCV RNA <25 IU/mL) 12 weeks after treatment ended 
      (SVR12). We collected data on on-treatment adverse events (AEs), serious AEs, and 
      laboratory abnormalities. RESULTS: All 20 patients completed 12 weeks of 
      treatment. Eighteen of the 20 patients achieved SVR12 (90%; 95% confidence 
      interval: 69.9-97.2). One patient death after the end of the treatment (unrelated 
      to the treatment) and 1 relapse accounted for the 2 non-SVRs. Adverse events were 
      primarily mild or moderate, and no patient discontinued treatment due to an AE. 
      Four patients experienced serious AEs; all were considered unrelated to 
      treatment. Ribavirin therapy was interrupted in 9 patients due to anemia; 4 
      received erythropoietin. No blood transfusions were performed. CONCLUSIONS: In a 
      clinical trial, the combination of ombitasvir, paritaprevir, and ritonavir, 
      administered with dasabuvir, led to an SVR12 in 90% of patients with HCV genotype 
      1 infection and stage 4 or 5 CKD. The regimen is well tolerated, though RBV use 
      may require a reduction or interruption to manage anemia. ClinicalTrials.gov ID 
      NCT02207088.
CI  - Copyright (c) 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.
FAU - Pockros, Paul J
AU  - Pockros PJ
AD  - Division of Gastroenterology/Hepatology, Scripps Clinic and Scripps Translational 
      Science Institute, La Jolla, California.
FAU - Reddy, K Rajender
AU  - Reddy KR
AD  - Division of Gastroenterology and Hepatology, University of Pennsylvania, 
      Philadelphia, Pennsylvania.
FAU - Mantry, Parvez S
AU  - Mantry PS
AD  - The Liver Institute at Methodist Dallas, Dallas, Texas.
FAU - Cohen, Eric
AU  - Cohen E
AD  - Infectious Disease Development, AbbVie Inc, North Chicago, Illinois.
FAU - Bennett, Michael
AU  - Bennett M
AD  - Medical Associates Research Group, San Diego, California.
FAU - Sulkowski, Mark S
AU  - Sulkowski MS
AD  - Division of Infectious Diseases and Gastroenterology/Hepatology, Johns Hopkins 
      University, Baltimore, Maryland.
FAU - Bernstein, David E
AU  - Bernstein DE
AD  - Division of Gastroenterology, North Shore University Hospital, Manhasset, New 
      York.
FAU - Cohen, Daniel E
AU  - Cohen DE
AD  - Infectious Disease Development, AbbVie Inc, North Chicago, Illinois.
FAU - Shulman, Nancy S
AU  - Shulman NS
AD  - Global Pharmaceutical Development, AbbVie Inc, North Chicago, Illinois.
FAU - Wang, Deli
AU  - Wang D
AD  - Statistics and Computer Sciences, AbbVie Inc, North Chicago, Illinois.
FAU - Khatri, Amit
AU  - Khatri A
AD  - Clinical Pharmacokinetics, AbbVie Inc, North Chicago, Illinois.
FAU - Abunimeh, Manal
AU  - Abunimeh M
AD  - Infectious Disease Development, AbbVie Inc, North Chicago, Illinois.
FAU - Podsadecki, Thomas
AU  - Podsadecki T
AD  - Global Pharmaceutical Development, AbbVie Inc, North Chicago, Illinois.
FAU - Lawitz, Eric
AU  - Lawitz E
AD  - Department of Gastroenterology, The Texas Liver Institute, University of Texas 
      Health Science Center, San Antonio, Texas. Electronic address: 
      lawitz@txliver.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT02207088
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
DEP - 20160311
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Anilides)
RN  - 0 (Antiviral Agents)
RN  - 0 (Carbamates)
RN  - 0 (Cyclopropanes)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Macrocyclic Compounds)
RN  - 0 (Sulfonamides)
RN  - 2302768XJ8 (ombitasvir)
RN  - 49717AWG6K (Ribavirin)
RN  - 56HH86ZVCT (Uracil)
RN  - 9DLQ4CIU6V (Proline)
RN  - CKR7XL41N4 (2-Naphthylamine)
RN  - DE54EQW8T1 (dasabuvir)
RN  - HG18B9YRS7 (Valine)
RN  - O3J8G9O825 (Ritonavir)
RN  - OU2YM37K86 (paritaprevir)
SB  - IM
MH  - 2-Naphthylamine
MH  - Aged
MH  - Anilides/administration & dosage
MH  - Antiviral Agents/*administration & dosage
MH  - Carbamates/administration & dosage
MH  - Cyclopropanes
MH  - Dose-Response Relationship, Drug
MH  - Drug Therapy, Combination
MH  - Female
MH  - Genotype
MH  - Hepacivirus/*genetics
MH  - Hepatitis C/complications/*drug therapy/virology
MH  - Humans
MH  - Kidney Failure, Chronic/*drug therapy/virology
MH  - Lactams, Macrocyclic
MH  - Macrocyclic Compounds/administration & dosage
MH  - Male
MH  - Middle Aged
MH  - Proline/analogs & derivatives
MH  - Prospective Studies
MH  - Ribavirin/administration & dosage
MH  - Ritonavir/administration & dosage
MH  - Sulfonamides/administration & dosage
MH  - Sustained Virologic Response
MH  - Uracil/administration & dosage/analogs & derivatives
MH  - Valine
OTO - NOTNLM
OT  - NS3/4A Protease Inhibitor
OT  - NS5A Inhibitor
OT  - RUBY-I
OT  - Renal Disease
EDAT- 2016/03/16 06:00
MHDA- 2017/05/23 06:00
CRDT- 2016/03/16 06:00
PHST- 2015/12/16 00:00 [received]
PHST- 2016/02/22 00:00 [revised]
PHST- 2016/02/25 00:00 [accepted]
PHST- 2016/03/16 06:00 [entrez]
PHST- 2016/03/16 06:00 [pubmed]
PHST- 2017/05/23 06:00 [medline]
AID - S0016-5085(16)00326-7 [pii]
AID - 10.1053/j.gastro.2016.02.078 [doi]
PST - ppublish
SO  - Gastroenterology. 2016 Jun;150(7):1590-1598. doi: 10.1053/j.gastro.2016.02.078. 
      Epub 2016 Mar 11.