PhagoBurn: the world first multicenter clinical study of phage therapy in serious burn victims
Launched in June 2013 and completed in January 2017, the European collaborative project PhagoBurn (www.phagoburn.eu) funded by the European Commission has evaluated the tolerance and effectiveness of bacteriophages to treat skin infections in burn victims. These infections caused by the bacterium Pseudomonas aeruginosa were susceptible or resistant to antibiotics. Treatment with phages was compared to the standard, silver sulfadiazine, an antibiotic used to treat skin infections.
In addition to the Health Service of the French Armies (Ministry of Defense) via the army training hospital Percy who coordinated the clinical phase, Queen Astrid military hospital (Brussels), Nantes and Liège University hospitals, CHR of Metz-Thionville and the Saint Joseph Saint Luc Hospital in Lyon included patients.
The patient inclusion period started on 22 July 2015 in seven burn centers located in France, Belgium and Switzerland and was completed in early January 2017. In this phase I / II randomized and controlled double-blind study, two mixtures (cocktails) of bacteriophages were evaluated against two bacteria present in the infections on burns: Pseudomonas aeruginosa and Escherichia coli. Nevertheless, the small number of patients infected with E. coli who could enter the clinical trial, led the partners to focus solely on treatment with anti-P. aeruginosa phage cocktail: PP1131. The lack of stability of PP1131 over time forced coordinators to discontinue the study from January to May 2016, thereby reducing the duration of the clinical study to a total of 13 months. Initially designed for a hundred patients per treatment, the study finally resulted in the recruitment of 27 patients, 25 of whom provided usable data. This low level of inclusion turned PhagoBurn into a clinical proof of concept.
Despite these difficulties, PhagoBurn remains a pillar clinical study to found modern phage therapy because the first conducted in compliance with international standards of clinical evaluation.
The results were published by The Lancet Infectious Disease in October 2018 under the title: Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double-blind phase 1/2 trial (https://www.sciencedirect.com/science/article/pii/S1473309918304821 ).
In summary, PP1131 cocktail was effective in 50% of the treated patients, despite the low dose administered on the infected burns. The action of phages was slower than that of silver sulfadiazine. An ancillary study showed that the isolated bacteria from patients who failed PP1131 treatment were resistant to the low doses of applied phages. Supporting antibiotics used to control other bacterial species had no impact on the effectiveness of each treatment.
PP1131 was very well tolerated and less often associated with serious adverse events: only one was reported with phages versus 4 with silver sulfadiazine.
PhagoBurn was partly funded by the 7 th Framework Program for Research and Development of the European Commission (HEALTH 2013,2,3,1 Drugs and vaccines for infections that have developed at risk of developing significant antimicrobial resistance).