London School of Hygiene & Tropical Medicine

Treating Ebola patients with plasma from recovered patients' blood is safe but it does not significantly improve their survival chances, according to the results of a major new trial published in the New England Journal of Medicine.

The Ebola-Tx trial is the largest ever conducted involving Ebola patients receiving convalescent plasma. It was carried out by an international research consortium which included the London School of Hygiene & Tropical Medicine and was led by the Institute of Tropical Medicine in Antwerp (ITM).

The study showed that treatment with convalescent plasma during an Ebola virus disease outbreak is feasible, safe and acceptable to donors, patients and health workers, but was unlikely to save lives.

However, the trial was planned, conducted and analysed in unusually fast time and demonstrates that it is possible to forge strong international research partnerships to conduct rapid, effective trials during major disease outbreaks in impoverished communities.

Professor Peter Smith, co-investigator from the London School of Hygiene & Tropical Medicine, said: "While it was not possible to conduct a randomised trial in the circumstances of the Ebola epidemic in Guinea, the results of this important study indicate that treatment with convalescent plasma from unselected Ebola survivors is unlikely to markedly improve Ebola survival rates.

"This treatment was relatively complicated to set up and administer and it is very disappointing that, despite these efforts, there was no significant impact on survival. We cannot exclude the possibility that selecting plasma donors with high levels of antibodies against the Ebola virus might be more effective, and this is a direction for future research."

Convalescent plasma was one of the possible interventions prioritised by the World Health Organization (WHO) during the crisis, as it had been used successfully to treat other viral diseases like measles, yellow fever and influenza. Until the 2014 outbreak, blood products from Ebola survivors had only been used as treatment experimentally in a small number of Ebola patients.

Tansy Edwards, co-investigator from the London School of Hygiene & Tropical Medicine, said: "Ebola-Tx is the largest controlled trial to investigate convalescent plasma from survivors as a therapeutic treatment for Ebola. This study demonstrates that it is possible to rapidly form a consortium of national and international research partners, and to conduct a treatment trial to a high standard in an emergency setting. The nature of the unprecedented outbreak meant that we had to design a trial that could be adapted to the evolving epidemic and address analytical challenges in the face of many uncertainties."

The trial took place between February and July 2015 at the Donka Ebola Treatment Centre in Conakry, Guinea, run by Médecins Sans Frontières (MSF). The survival rate of the 84 patients included in the trial was compared to that of over 400 patients who had been treated in the same centre in the five months preceding the trial.

Patients of any age with confirmed Ebola virus disease (including pregnant women) received two units of 200-250ml of plasma from different convalescent donors within 48 hours after laboratory confirmed diagnosis, as recommended by the WHO. Mortality was 31% in the group with the virus and 37.8% in the comparator group; but the difference was reduced to only 2.6% after adjusting for age and viral load.

Prof Johan van Griensven of ITM Antwerp said: "A single administration of two units of convalescent plasma does not save lives, but further analysis may reveal whether the amount of antibodies in the donated plasma had an impact on treatment outcomes. Possibly, a more targeted and concentrated use of plasma could help patients fight off Ebola. Although these results might not be the answer we had hoped for, they provide crucial information about the role of convalescent plasma against this horrible disease."

The samples have been shipped to France for analysis in a high containment laboratory and the researchers expect to present additional findings in the coming months. This may indicate whether plasma with high levels of antibodies is more effective.

Publication

• Johan van Griensven, Tansy Edwards, Xavier de Lamballerie, Malcolm G. Semple, Pierre Gallian, Sylvain Baize, Peter W. Horby, Hervé Raoul, N'Faly Magassouba, Annick Antierens, Carolyn Lomas, Ousmane Faye, Amadou A. Sall, Katrien Fransen, Jozefien Buyze, Raffaella Ravinetto, Pierre Tiberghien, Yves Claeys, Maaike De Crop, Lutgarde Lynen, Elhadj Ibrahima Bah, Peter G. Smith, Alexandre Delamou, Anja De Weggheleire, and Nyankoye Haba for the Ebola-Tx Consortium. Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea. New England Journal of Medicine. DOI: 10.1056/NEJMoa1511812