Nav: Home

Nuanced findings for a large experimental treatment trial for Ebola virus disease

March 01, 2016

While not conclusive, valuable research generated through researching an experimental treatment for Ebola virus disease in Guinea during the recent Ebola outbreak will support future research into treating Ebola virus disease, according to Prof. Denis Malvy from INSERM, France and a large team of international researchers in a new Research Article published in this week's PLOS Medicine.

Ebola virus disease is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the recent Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for Ebola virus disease research that included favipiravir, an antiviral developed for the treatment of severe influenza. To test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak and to collect preliminary data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with Ebola virus disease, a multinational team of researchers conducted a study in Guinea called JIKI (meaning "Hope" in the Malinke language). Because of the exceptional circumstances of the recent Ebola outbreak the study was a historically controlled multicenter non-randomized trial, in which all 126 participants received favipiravir along with standardized care.

The results of the study indicate that monotherapy with favipiravir is unlikely to be effective in patients with very high viremia (Ebola virus in the blood) and merits further investigation in patients with intermediate to high viremia. This conclusion is based on two findings, namely, the observed mortality rates and the dynamics of Ebola virus RNA measured in the blood of patients on treatment. In patients with very high viremia, mortality was 7% higher than expected based on historical Ebola cases and Ebola virus measurements did not decrease. This suggests that any future trial is unlikely to demonstrate any benefit of favipiravir in these patients. In patients with lower viremia, mortality was 33% lower than expected based on historical controls and viremia decreased rapidly on treatment but the study was not able to attribute this decrease to favipiravir. The trial was non-randomized and the 95% confidence interval of mortality overlapped with what was expected from historical Ebola patients. Therefore, this finding does not prove that favipiravir was effective in these patients but only suggests that the question remains open and gives some indication on how to better address it.

The authors conclude, "[i]n the midst of an Ebola outbreak, researchers may be faced with elements that make them feel that randomizing patients to receive either standard care or standard care plus an experimental drug is not ethically acceptable. In these rare circumstances, it can be decided to not run a trial and to wait for more favorable conditions, or to run a non-randomized trial. In this pilot experience, we did the latter. Our conclusions are nuanced. On the one hand, we cannot conclude on the efficacy of the drug, and our conclusions on tolerance, although encouraging, cannot be as firm as they would have been if we could have used randomization. On the other hand, we learned a lot about how to quickly set up and run a trial in such unusual circumstances and in close relationship with the community and non-governmental organizations, we integrated research into care so that it improved care, we rapidly generated and shared with the scientific community intermediate data that were useful for designing Ebola research, and we gathered evidence that will allow researchers to base further trials on strong preliminary assumptions."
Research Article


The JIKI trial was supported by grants from the French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France), the French Institute for Health Research (Inserm, Paris, France) and the European Union (Horizon 2020 programme, grant N° 666092 REACTION and N° 666100 EVIDENT; European Commission's Directorate-General for International Cooperation and Development, service contract IFS/2011/272-372). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests:

I have read the journal's policy and the authors of this manuscript have the following competing interests: SB, XdL, HR, and SG received a grant from St Luke International University (Tokyo, Japan) to perform research on favipiravir in non-human primates. YY declared board membership for AbbVie, BMS, Gilead, MSD, Roche, Johnson&Johnson, ViiV Healthcare, Pfizer, and consultancy for AbbVie, BMS, Gilead, MSD, Roche, Johnson&Johnson, ViiV Healthcare, and Pfizer. OP worked for Fab'entech biotechnology from 1st April to 13th November 2015. Between January 2014 and now, SC received a grant from the CHU de Québec research center, which had no relationship with the trial described in the paper. All other authors declared no conflict of interest.


Sissoko D, Laouenan C, Folkesson E, M'Lebing A-B, Beavogui A-H, Baize S, et al. (2016) Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea. PLoS Med 13(3): e1001967. doi:10.1371/journal.pmed.1001967

Author Affiliations:

Inserm, UMR 1219, Université de Bordeaux, Bordeaux, France
Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
Inserm, IAME, UMR 1137, Université Paris Diderot, Paris, France
Assistance Publique-Hôpitaux de Paris, Hôpital Bichat Claude Bernard, Paris, France
Médecins Sans Frontières Belgique, Brussels, Belgium
ALIMA, Dakar, Senegal
Centre de Recherche en Santé Rurale, Maférinya, Guinea
Institut Pasteur, Centre International de Recherche en Infectiologie, Lyon, France
Inserm, Laboratoire P4 Jean Mérieux, Lyon, France
European Mobile Laboratory Project, Hamburg, Germany
Rega Institute for Medical Research, Leuven, Belgium
Programme PACCI, Abidjan, Côte d'Ivoire
Biological Light Fieldable Laboratory for Emergencies (B-LiFE)/Belgian First Aid and Support (B-FAST), Brussels, Belgium
Cliniques Universitaires Saint-Luc, Brussels, Belgium
Université Catholique de Louvain, Louvain-la-Neuve, Belgium
Belgian Ministry of Defense, Brussels, Belgium
Croix Rouge Française, Paris, France
Service de Santé des Armées, Paris, France
Institut National de Santé Publique, Conakry, Guinea
Laboratoire des Fièvres Hémorragiques en Guinée, Université Gamal Abdel Nasser de Conakry, Conakry, Guinea
Ecole Normale Supérieure, Lyon, France
Friedrich Loeffler Institute-Federal Research Institute for Animal Health, Greifswald, Germany
Robert Koch Institute, Berlin, Germany
Public Health Agency of Sweden, Solna, Sweden
Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France
Université de Montréal, Québec, Montréal, Canada
Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Paris, France
Public Health England, Porton Down, United Kingdom
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy
Bundeswehr Institute of Microbiology, Munich, Germany
Solidarité Thérapeutique et Initiatives pour la Santé (Solthis), Paris, France
Inserm, Paris, France
Southampton General Hospital, University of Southampton, Southampton, United Kingdom
Centre Hospitalier Universitaire de Treichville, Abidjan, Côte d'Ivoire
Université Aix Marseille, Institut de Recherche pour le Développement, École des Hautes Études en Santé Publique, EPV, Marseille, France
Cellule de Coordination Nationale de Lutte contre la Maladie à Virus Ebola Conakry, Guinea



Denis Malvy
CHU de Bordeaux
146 rue Léo Saignat
Bordeaux, 33076
+33 5 57 57 17 65
FAX: +33 5 57 57 45 28


Related Mortality Articles:

New analysis shows hydroxychloroquine does not lower mortality in COVID-19 patients, and is associated with increased mortality when combined with the antibiotic azithromycin
A new meta-analysis of published studies into the drug hydroxychloroquine shows that it does not lower mortality in COVID-19 patients, and using it combined with the antibiotic azithromycin is associated with a 27% increased mortality.
Hydroxychloroquine reduces in-hospital COVID-19 mortality
An Italian observational study contributes to the ongoing debate regarding the use of hydroxychloroquine in the current pandemic.
What's the best way to estimate and track COVID-19 mortality?
When used correctly, the symptomatic case fatality ratio (sCFR) and the infection fatality ratio (IFR) are better measures by which to monitor COVID-19 epidemics than the commonly reported case fatality ratio (CFR), according to a new study published this week in PLOS Medicine by Anthony Hauser of the University of Bern, Switzerland, and colleagues.
COVID-19: Bacteriophage could decrease mortality
Bacteriophage can reduce bacterial growth in the lungs, limiting fluid build-up.
COPD and smoking associated with higher COVID-19 mortality
Current smokers and people with chronic obstructive pulmonary disease (COPD) have an increased risk of severe complications and higher mortality with COVID-19 infection, according to a new study published May 11, 2020 in the open-access journal PLOS ONE by Jaber Alqahtani of University College London, UK, and colleagues.
Highest mortality risks for poor and unemployed
Large dataset shows that income, work status and education have a clear influence on mortality in Germany.
Addressing causes of mortality in Zambia
Despite the fact that people in sub-Saharan Africa are now living longer than they did two decades ago, their average life expectancy remains below that of the rest of the world population.
Examining the link between caste and under-five mortality in India
In India, children that belong to disadvantaged castes face a much higher likelihood of not living past their fifth birthday than their counterparts in non-deprived castes.
Mortality rates rising for Gens X and Y too
Declining life expectancies in the US include Gen X and Y Americans, in addition to the older Baby Boomers.
Trust in others predicts mortality in the United States
Do you trust other people? It may prolong your life.
More Mortality News and Mortality Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at     You can read The Transition Integrity Project's report here.