Evidence map›Paper›PMID 28231247›Full record

Trial reportPLoS neglected tropical diseases2017

Favipiravir pharmacokinetics in Ebola-Infected patients of the JIKI trial reveals concentrations lower than targeted.

Thi Huyen Tram Nguyen, Jérémie Guedj, Xavier Anglaret, Cédric Laouénan, Vincent Madelain, Anne-Marie Taburet, Sylvain Baize, Daouda Sissoko, Boris Pastorino, Anne Rodallec and 12 more

Registry-linked trialAbstract readClinical Trial
In one paragraph

Trial report in PLoS neglected tropical diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02329054 (Efficacy of Favipiravir in Reducing Mortality in Individuals With Ebola Virus Disease in Guinea), which is not on this map. Cited by 93 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 4 pooled it
–field-weighted citation impact
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.

NCT02329054 phase2completednot on this map

Efficacy of Favipiravir in Reducing Mortality in Individuals With Ebola Virus Disease in Guinea

TypeinterventionalSponsorInstitut National de la Santé Et de la Recherche Médicale, FranceRan2014 to 2015Enrolled126ConditionsEbola Virus DiseaseArmsFavipiravir
3 · Its place in the literature

Who cites it

93 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. The efficacy and adverse effects of favipiravir on patients with COVID-19: A systematic review and meta-analysis of published clinical trials and observational studies.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2022
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  10. Randomized controlled open label trial on the use of favipiravir combined with inhaled interferon beta-1b in hospitalized patients with moderate to severe COVID-19 pneumonia.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2021
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33 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Thi Huyen Tram NguyenINSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
Jérémie GuedjINSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.ORCID 0000-0002-5534-5482
Xavier AnglaretInserm, UMR 1219, Université de Bordeaux, Bordeaux, France.
Cédric LaouénanINSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.ORCID 0000-0002-3681-6314
Vincent MadelainINSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
Anne-Marie TaburetAssistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Paris, France and Inserm UMR1184, Université Paris-Sud.
Sylvain BaizeUBIVE, Institut Pasteur, Centre International de Recherche en Infectiologie, Lyon, France.
Daouda SissokoInserm, UMR 1219, Université de Bordeaux, Bordeaux, France.ORCID 0000-0002-8890-7170
Boris PastorinoUniversité Aix Marseille, Institut de Recherche pour le Développement, École des Hautes Études en Santé Publique, EPV, Marseille, France.
Anne RodallecUniversité Aix Marseille, Institut de Recherche pour le Développement, École des Hautes Études en Santé Publique, EPV, Marseille, France.
Géraldine PiorkowskiUniversité Aix Marseille, Institut de Recherche pour le Développement, École des Hautes Études en Santé Publique, EPV, Marseille, France.
Sara CarazoMédecins Sans Frontières Belgique, Brussels, Belgium.ORCID 0000-0003-0711-6703
Mamoudou N CondeALIMA, Dakar, Senegal.
Jean-Luc GalaBiological Light Fieldable Laboratory for Emergencies (B-LiFE)/Belgian First Aid and Support (B-FAST), Brussels, Belgium.ORCID 0000-0002-7749-573X
Joseph Akoi BoreEuropean Mobile Laboratory Project, Hamburg, Germany.
Caroline CarbonnelleInserm, Laboratoire P4 Jean Mérieux, Lyon, France.
Frédéric JacquotInserm, Laboratoire P4 Jean Mérieux, Lyon, France.
Hervé RaoulInserm, Laboratoire P4 Jean Mérieux, Lyon, France.
Denis MalvyInserm, UMR 1219, Université de Bordeaux, Bordeaux, France.
Xavier de LamballerieUniversité Aix Marseille, Institut de Recherche pour le Développement, École des Hautes Études en Santé Publique, EPV, Marseille, France.ORCID 0000-0001-7895-2720
France MentréINSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
JIKI study group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn 2014-2015, we assessed favipiravir tolerance and efficacy in patients with Ebola virus (EBOV) disease (EVD) in Guinea (JIKI trial). Because the drug had never been used before for this indication and that high concentrations of the drugs were needed to achieve antiviral efficacy against EBOV, a pharmacokinetic model had been used to propose relevant dosing regimen. Here we report the favipiravir plasma concentrations that were achieved in participants in the JIKI trial and put them in perspective with the model-based targeted concentrations. METHODS AND

findingsPre-dose drug concentrations were collected at Day-2 and Day-4 of treatment in 66 patients of the JIKI trial and compared to those predicted by the model taking into account patient's individual characteristics. At Day-2, the observed concentrations were slightly lower than the model predictions adjusted for patient's characteristics (median value of 46.1 versus 54.3 μg/mL for observed and predicted concentrations, respectively, p = 0.012). However, the concentrations dropped at Day-4, which was not anticipated by the model (median values of 25.9 and 64.4 μg/mL for observed and predicted concentrations, respectively, p<10-6). There was no significant relationship between favipiravir concentrations and EBOV viral kinetics or mortality.

conclusionsFavipiravir plasma concentrations in the JIKI trial failed to achieve the target exposure defined before the trial. Furthermore, the drug concentration experienced an unanticipated drop between Day-2 and Day-4. The origin of this drop could be due to severe sepsis conditions and/or to intrinsic properties of favipiravir metabolism. Dose-ranging studies should be performed in healthy volunteers to assess the concentrations and the tolerance that could be achieved with high doses.

trial registrationClinicalTrials.gov NCT02329054.

Indexed as

AdolescentAdultAgedAmidesAntiviral AgentsChildChild, PreschoolEbolavirusFemaleGuineaHemorrhagic Fever, EbolaHumansMaleMiddle AgedPyrazinesYoung AdultAmidesAntiviral AgentsfavipiravirPyrazines

Identifiers

PMID28231247
PMCPMC5340401

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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.