PMID- 31216086
OWN - NLM
STAT- MEDLINE
DCOM- 20200716
LR  - 20200716
IS  - 1365-2893 (Electronic)
IS  - 1352-0504 (Linking)
VI  - 26
IP  - 10
DP  - 2019 Oct
TI  - Deferred treatment with a fixed-dose combination of sofosbuvir-velpatasvir for 
      chronic hepatitis C virus genotype 1, 2, 4 and 6 infection.
PG  - 1229-1232
LID - 10.1111/jvh.13159 [doi]
AB  - Sofosbuvir-velpatasvir is approved for the treatment of chronic hepatitis C virus 
      (HCV) infection. In this single-arm, open-label, phase 3, deferred treatment 
      study, we investigated the efficacy and safety of sofosbuvir-velpatasvir among 
      patients randomized to the placebo group in the ASTRAL-1 study. Patients received 
      sofosbuvir-velpatasvir (400/100 mg) once daily for 12 weeks. The primary efficacy 
      endpoint was the proportion of patients with sustained virologic response 
      12 weeks after the end of therapy (SVR12). The primary safety endpoint was any 
      adverse events (AEs) leading to the permanent discontinuation of study drug. 
      Overall, 108/111 (97%, 95% confidence interval [CI], 92%-99%) achieved SVR12, and 
      only one patient had virological failure. SVR12 was achieved by 61/63 (97%, 
      95%CI, 89%-100%) genotype 1 patients, 20/20 (100%; 95%CI, 83%-100%) with genotype 
      2, 19/19 (100%; 95%CI, 82%-100%) with genotype 4 and 8/9 (89%; 95% CI, 52%-100%) 
      with genotype 6. All (19/19; 95%CI, 82-100) patients with cirrhosis and all 
      (31/31, 95%CI, 89-100) with prior treatment experience achieved SVR12. The safety 
      profile during treatment was similar to that observed in patients receiving 
      placebo treatment. The most common AEs were headache, fatigue and nausea. One 
      patient (1%) discontinued treatment due to an AE of gallbladder carcinoma, which 
      was not considered related to treatment. Of five reported serious AEs, none were 
      considered related to study drug. Sofosbuvir-velpatasvir for 12 weeks was 
      effective and well tolerated among untreated and previously treated patients with 
      HCV genotype 1, 2, 4 or 6 infection, including those with compensated cirrhosis 
      (ClinicalTrials.gov NCT02346721).
CI  - (c) 2019 John Wiley & Sons Ltd.
FAU - Asselah, Tarik
AU  - Asselah T
AUID- ORCID: 0000-0002-0024-0595
AD  - Hepatology Department, Head of Viral Hepatitis Team, INSERM UMR1149, Beaujon 
      Hospital, Universite Paris Diderot, Paris, France.
FAU - Shafran, Stephen D
AU  - Shafran SD
AD  - University of Alberta, Edmonton, Canada.
FAU - Bourgeois, Stefan
AU  - Bourgeois S
AD  - Ziekenhuis Netwerk Antwerpen STER Site Stuivenberg, Antwerpen, Belgium.
FAU - Lai, Ching-Lung
AU  - Lai CL
AD  - The University of Hong Kong, Hong Kong.
FAU - Mathurin, Philippe
AU  - Mathurin P
AD  - Hopital Claude Huriez, Lille, France.
FAU - Willems, Bernard
AU  - Willems B
AD  - Universite de Montreal, Quebec, Canada.
FAU - Nguyen, Mindie H
AU  - Nguyen MH
AUID- ORCID: 0000-0002-6275-4989
AD  - Stanford University Medical Center, Stanford, California, USA.
FAU - Davis, Mitchell N
AU  - Davis MN
AD  - South Florida Center of Gastroenterology, Wellington, Florida, USA.
FAU - Huang, K C
AU  - Huang KC
AD  - Gilead Sciences, Inc, Foster City, California, USA.
FAU - Svarovskaia, Evguenia
AU  - Svarovskaia E
AD  - Gilead Sciences, Inc, Foster City, California, USA.
FAU - Osinusi, Anu
AU  - Osinusi A
AD  - Gilead Sciences, Inc, Foster City, California, USA.
FAU - McNally, John
AU  - McNally J
AD  - Gilead Sciences, Inc, Foster City, California, USA.
FAU - Brainard, Diana M
AU  - Brainard DM
AD  - Gilead Sciences, Inc, Foster City, California, USA.
FAU - Shaikh, Obaid S
AU  - Shaikh OS
AD  - VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.
FAU - Tran, Tram T
AU  - Tran TT
AD  - Cedars-Sinai Medical Center, Los Angeles, California, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02346721
PT  - Clinical Trial, Phase III
PT  - Controlled Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190804
PL  - England
TA  - J Viral Hepat
JT  - Journal of viral hepatitis
JID - 9435672
RN  - 0 (Antiviral Agents)
RN  - 0 (Carbamates)
RN  - 0 (Drug Combinations)
RN  - 0 (Heterocyclic Compounds, 4 or More Rings)
RN  - 0 (Placebos)
RN  - KCU0C7RS7Z (velpatasvir)
RN  - WJ6CA3ZU8B (Sofosbuvir)
SB  - IM
MH  - Antiviral Agents/*administration & dosage/adverse effects
MH  - Carbamates/*administration & dosage/adverse effects
MH  - *Drug Combinations
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology
MH  - Female
MH  - *Genotype
MH  - Hepacivirus/*classification/genetics/isolation & purification
MH  - Hepatitis C, Chronic/*drug therapy/virology
MH  - Heterocyclic Compounds, 4 or More Rings/*administration & dosage/adverse effects
MH  - Humans
MH  - Male
MH  - Placebos/administration & dosage
MH  - Sofosbuvir/*administration & dosage/adverse effects
MH  - Sustained Virologic Response
MH  - Treatment Outcome
OTO - NOTNLM
OT  - NS5A inhibitor
OT  - NS5B inhibitor
OT  - direct-acting antivirals
OT  - pangenotypic activity
EDAT- 2019/06/20 06:00
MHDA- 2020/07/17 06:00
CRDT- 2019/06/20 06:00
PHST- 2018/12/18 00:00 [received]
PHST- 2019/03/29 00:00 [revised]
PHST- 2019/05/15 00:00 [accepted]
PHST- 2019/06/20 06:00 [pubmed]
PHST- 2020/07/17 06:00 [medline]
PHST- 2019/06/20 06:00 [entrez]
AID - 10.1111/jvh.13159 [doi]
PST - ppublish
SO  - J Viral Hepat. 2019 Oct;26(10):1229-1232. doi: 10.1111/jvh.13159. Epub 2019 Aug 
      4.