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.

The overall objective of the study was to evaluate the safety and efficacy of treatment with anti-influenza immune plasma in addition to standard care in subjects with influenza. The primary efficacy endpoint chosen was normalization of tachypnea or hypoxia defined as normalization of both respiratory rate (≤ 20 for adults, or below the age defined thresholds of 20-38 for children), and room air saturation of oxygen (SaO2) ≥93%. The secondary endpoints included: incidence and duration of clinical symptoms, incidence and duration of fever, time to resolution of all symptoms and fever, in-hospital, and 28-day mortality, duration of hospitalization, number of admissions and duration of admission to an intensive care unit, incidence and duration of supplemental oxygen, incidence of ARDS, incidence and duration of requiring mechanical ventilation, and disposition (home with no health care, home with health care, transferred to long-term care facility, hospitalization ongoing at Day 28, discharged to hospice care, deceased) following the last hospital discharge. All secondary analysis including subgroups were pre-specified in a formal Statistical Analysis Plan with the exception of the 6-step ordinal scale of clinical status at Day 7, which was developed for a separate anti-influenza IVIG study (ClinicalTrials.gov Identifier: NCT02287467) and was used post-hoc in this study.