Ebola-Tx trial delivers results
Treatment with convalescent plasma during an Ebola virus disease outbreak is feasible, safe to use and acceptable to donors, patients and health workers, the results of the EU-funded Ebola-Tx trial have shown.
However, the treatment as given in the trial did not significantly improve the survival chances of Ebola patients. Levels of neutralising antibodies against the Ebola virus in the donor plasma used on the trial could not be determined before administration, as tests to measure these antibodies were not available on site. Samples have been shipped to France for analysis, and the researchers expect to present additional findings in the coming months which may indicate whether plasma with high levels of antibodies is more effective.
Until the 2014 outbreak, blood products from Ebola survivors had only been used as treatment experimentally in a handful of Ebola patients. The Ebola-Tx trial, led by the Antwerp Institute of Tropical Medicine (ITM), is the largest ever trial of convalescent plasma for the treatment of Ebola.
A total of 102 patients were enrolled in the trial, which took place between February and July 2015 at the Donka Ebola Treatment Centre in Conakry, Guinea, run by Médecins Sans Frontières (MSF). Patients of any age with confirmed Ebola virus disease (including pregnant women) received two 200-250ml units from different convalescent donors within 48 hours after laboratory-confirmed diagnosis, as recommended by the World Health Organization. The levels of Ebola virus neutralising antibodies in the plasma were unknown at the time of administration.
Patients presenting to the same treatment centre in the five months preceding the trial served as the comparator group. The primary outcome was survival 14 days after transfusion, adjusted for age and the amount of Ebola virus in the blood at diagnosis, excluding deaths occurring up to two days after the diagnosis of Ebola virus disease. A 20% lower mortality in the group treated with convalescent plasma was considered a clinically important difference.
A total of 84 patients treated with convalescent plasma and 418 comparator patients were included in the analysis. Mortality from day three to day 16 was 31% in the convalescent plasma group and 37.8% in the comparator group, but the difference was reduced to only 2.6% after adjusting for age and viral load. During the course of the study, all newly admitted patients at the Donka centre consented to take part. No severe adverse reactions to convalescent plasma were observed.
Commenting on these results, co-ordinating investigator Professor 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. We now also know this kind of intervention can be safely organised in an emergency situation.”
Dr Ruxandra Draghia-Akli, director of the Health Directorate at the European Commission, added: “The results announced today by the Ebola-Tx project provide the answer to an important gap in our knowledge about the Ebola virus and are complementary to the existing portfolio of EU-funded projects.
“Even though the treatment studied proved to be ineffective in treating Ebola, we strongly encourage specialised journals to keep publishing this type of findings as an explicit example of health research for the benefit of patients worldwide. We applaud the consortium’s success to perform a clinical trial under the challenging conditions imposed by the Ebola outbreak. This achievement belongs to the utmost extent to the people of Guinea, the Ebola survivors who came forward to donate blood, and to the local communities that supported this research effort.”
The results have been published in the New England Journal of Medicine.
