A Randomized Study of Immune Plasma for the Treatment of Severe Influenza

Beigel, John H.; Tebas, Pablo; Elie-Turenne, Marie-Carmelle; Bajwa, Ednan; Bell, Todd E.; Cairns, Charles B.; Shoham, Shmuel; Deville, Jaime G.; Feucht, Eric; Feinberg, Judith; Luke, Thomas; Raviprakash, Kanakatte; Danko, Janine; O’Neil, Dorothy; Metcalf, Julia A.; King, Karen; Burgess, Timothy H.; Aga, Evgenia; Lane, H. Clifford; Hughes, Michael D.; Davey, Richard T.

Pandemic influenza remains a global health threat. In the setting of an outbreak, there is a need for new countermeasures that can be rapidly implemented. Plasma therapy has been used experimentally for the last 100 years to treat severe infectious diseases beginning with diphtheria in the 1890's, Spanish flu of 1917-1918, and severe acute respiratory syndrome (SARS) in 2003, Middle East respiratory syndrome (MERS), and most recently, the Ebola epidemic in West Africa. A meta-analysis of 8 non-randomized studies using convalescent blood products during the 1918 influenza pandemic calculated a case-fatality rate of 16% among 336 treated participants compared to 37% among 1219 controls. [1] A cohort study of 93 participants with severe H1N1 influenza demonstrated lower mortality in the treatment group receiving H1N1 convalescent plasma vs the control group (20·0% vs. 54·8%; P = .01), [2] although mortality in the control group was higher than expected for comparable severity of illness. [3] [4] [5] [6] Despite these encouraging data, no randomized controlled trial (RCT) of immune plasma for severe influenza has ever been conducted. In an effort to more rigorously evaluate the role of immune plasma in the treatment of severe influenza we conducted a RCT in a non-pandemic setting in participants with respiratory compromise due to influenza.