Evidence map›Paper›PMID 25591505›Full record

Trial reportLancet (London, England)2015

Virological response after 6 week triple-drug regimens for hepatitis C: a proof-of-concept phase 2A cohort study.

Anita Kohli, Anuoluwapo Osinusi, Zayani Sims, Amy Nelson, Eric G Meissner, Lisa L Barrett, Dimitra Bon, Miriam M Marti, Rachel Silk, Colleen Kotb and 27 more

Registry-linked trialAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Lancet (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01805882 (A Pilot Study to Evaluate the Safety and Efficacy of Multiple Anti-HCV Combination Therapy in Chronically Infected Hepatitis C Patients), which is not on this map. Cited by 79 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 1 pooled it
16.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01805882 phase2completednot on this map

A Pilot Study to Evaluate the Safety and Efficacy of Multiple Anti-HCV Combination Therapy in Chronically Infected Hepatitis C Patients

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2013 to 2015Enrolled229ConditionsHepatitis C, ChronicArmsSofosbuvir, Ledipasvir, GS-9669, GS-9451
3 · Its place in the literature

Who cites it

79 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.

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  4. Peripheral PD-1Frontiers in immunology · 2019
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  11. Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016
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  16. Utility of hepatitis C viral load monitoring on direct-acting antiviral therapy.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2015
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19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

37 authors at 10 institutions in 3 countries.

Anita KohliCritical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA; Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Anuoluwapo OsinusiClinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA; Department of Medicine, Dalhousie University, Halifax, NS, Canada.
Zayani SimsCritical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Amy NelsonLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA.
Eric G MeissnerLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA.
Lisa L BarrettLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA; Department of Medicine, Dalhousie University, Halifax, NS, Canada.
Dimitra BonInstitute of Biostatistics and Mathematical Modeling, Johann Wolfgang Goethe University, Frankfurt, Germany.
Miriam M MartiLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA.
Rachel SilkClinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Colleen KotbClinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Chloe GrossClinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Tim A JolleyLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA.
Sreetha SidharthanCritical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Tess PetersenCritical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Kerry TownsendLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA.
D'Andrea EgersonClinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Rama KapoorClinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Emily SpurlinLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA.
Michael SnellerLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA.
Michael ProschanBiostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA.
Eva HerrmannInstitute of Biostatistics and Mathematical Modeling, Johann Wolfgang Goethe University, Frankfurt, Germany.
Richard KwanLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA.
Gebeyehu TeferiUnity Health Care, Washington DC, USA.
Rohit TalwaniDivision of Infectious Diseases, Institute of Human Virology, University of Maryland, MD, USA.
Gabbie DiazClinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA; The National Cancer Institute, National Institutes of Health, MD, USA.
David E KleinerLaboratory of Pathology, National Cancer Institute, MD, USA.
Brad J WoodCenter for Interventional Oncology, Radiology and Imaging Sciences, NIH Clinical Center and National Cancer Institute, MD, USA.
Jose ChavezUnity Health Care, Washington DC, USA.
Stephen AbbottUnity Health Care, Washington DC, USA.
William T SymondsGilead Sciences, CA, USA.
G Mani SubramanianGilead Sciences, CA, USA.
Phillip S PangGilead Sciences, CA, USA.
John McHutchisonGilead Sciences, CA, USA.
Michael A PolisLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA.
Anthony S FauciLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA.
Henry MasurCritical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Shyam KottililLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MD, USA. Electronic address: skottilil@niaid.nih.gov.
National Institutes of Health · USNational Institutes of Health Clinical Center · USFrederick National Laboratory for Cancer Research · USGilead Sciences (United States) · USNational Institute of Allergy and Infectious Diseases · USLeidos (United States) · USGoethe University Frankfurt · DENational Cancer Institute · USDalhousie University · CAUniversity of Maryland, Baltimore · US

Funding

Center for Interventional OncologyZIDBC011242 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WOOD, BRADFORD J · 2009 to 2025
$18.7M
Therapeutic Strategies for the Management of HCV/HIV co- infectionZ01AI000390 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI FAUCI, ANTHONY S. · 1985 to 2008
$348k
DC Partnership for HIV/AIDS Progress (DC PFAP)ZIACL009010 · CLC · CLINICAL CENTER · PI MASUR, HENRY · 2010 to 2025
$0k
Interventional OncologyZIACL040015 · CLC · CLINICAL CENTER · PI WOOD, BRADFORD · 2009 to 2025
$0k
CCR NIH HHS HHSN261200800001CIntramural NIH HHS Z01 AI000390NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

backgroundDirect-acting antiviral drugs have a high cure rate and favourable tolerability for patients with hepatitis C virus (HCV). Shorter courses could improve affordability and adherence. Sofosbuvir and ledipasvir with ribavirin have high efficacy when taken for 8 weeks but not for 6 weeks. We assessed whether the addition of a third direct-acting antiviral drug to sofosbuvir and ledipasvir would allow a shorter treatment duration.

methodsIn this single-centre, open-label, phase 2A trial, we sequentially enrolled treatment-naive patients with HCV genotype 1 infection into three treatment groups: 12 weeks of sofosbuvir and ledipasvir; 6 weeks of sofosbuvir, ledipasvir, and GS-9669; or 6 weeks of sofosbuvir, ledipasvir, and GS-9451. Patients and investigators were not masked to treatment assignment. The primary endpoint was the propotion of patients with sustained viral response at 12 weeks after treatment completion (SVR12), assessed by serum HCV RNA concentrations lower than 43 IU/mL (the lower limit of quantification). We did an intention-to-treat analysis for the primary endpoint and adverse events. This study is registered with ClinicalTrials.gov, number NCT01805882.

findingsBetween Jan 11, 2013, and Dec 17, 2013, we enrolled 60 patients, and sequentially assigned them into three groups of 20. We noted an SVR12 in all 20 patients (100%, 95% CI 83-100) allocated to sofosbuvir and ledipasvir for 12 weeks; in 19 (95%, 75-100) of the 20 patients allocated to sofosbuvir, ledipasvir, and GS-9669 for 6 weeks (one patient relapsed 2 weeks after completion of treatment); and in 19 (95%, 75-100%) of the 20 patients allocated to sofosbuvir, ledipasvir, and GS-9451 for 6 weeks (one patient was lost to follow-up after reaching sustained viral response at 4 weeks). Most adverse events were mild and no patients discontinued treatment. Two serious adverse events occurred (pain after a post-treatment liver biopsy and vertigo), both unrelated to study drugs.

interpretationIn this small proof-of-concept study, two different three-drug regimens that were given for 6 weeks resulted in high cure rates for HCV infection with excellent tolerability. Addition of a third potent direct-acting antiviral drug can reduce the duration of treatment required to achieve sustained viral response in patients with chronic HCV genotype 1 infection without cirrhosis.

fundingNational Institute of Allergy and Infectious Diseases (NIAID), National Cancer Institute and Clinical Center Intramural Program, German Research Foundation, National Institutes of Health, Gilead Sciences.

Indexed as

AgedAntiviral AgentsBenzimidazolesCohort StudiesDrug Therapy, CombinationFemaleFluorenesFuransHepacivirusHepatitis C, ChronicHumansIntention to Treat AnalysisMaleMiddle AgedQuinolinesRibavirinAntiviral AgentsBenzimidazolesFluorenesFuransGS-9451GS-9669ledipasvirQuinolinesRibavirinRNA, ViralSofosbuvirThiophenesUridine Monophosphate

Identifiers

PMID25591505
PMCPMC4427052
OpenAlexW2151063300

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.