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.

Hospitalized participants with influenza A(H1N1), A(H3N2) or B virus infections (diagnosed locally by rapid antigen or polymerase chain reaction (PCR)) who had either hypoxia (room air saturation of oxygen < 93%) or tachypnea (respiratory rate greater than 20 for adults, or age defined thresholds of between 20 and 38 for children) were eligible for enrollment. The study initially was restricted to onset of illness within 7 days, but subsequently revised to allow participants to be enrolled regardless of onset time if there was active viral replication (as evidenced by a positive diagnostic test). The study initially enrolled participants with influenza H1N1 only, but was amended to also include influenza H3N2 and B. Participants were excluded if ABO compatible plasma was not available, if the participant had received investigational antivirals in the prior 2 weeks, if they had a history of any allergic reactions to blood products, if they had medical conditions in which they could not tolerate 500 mL volume, or if there was a clinical suspicion that the etiology of acute illness was primarily due to a condition other than active influenza virus replication (e.g. primarily a bacterial superinfection). Per protocol, only non-pregnant adults were enrolled in the first year. Subsequently, after Data and Safety Monitoring Board (DSMB) review of interim data, children and pregnant women were also made eligible for enrollment.