Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study

• Type of Material: Article
• Authors: John D Roback, Emory University; Jonathan Sevransky, Emory University; John H. Beigel, Leidos Biomedical Research, Inc.; Pablo Tebas, University of Pennsylvania; Ednan Bajwa, Massachusetts General Hospital; Marie-Carmelle Elie-Turenne, University of Florida; Todd E. Bell, Texas Tech University Health Sciences Center; Charles B. Cairns, University of North Carolina at Chapel Hill; Shmuel Shoham, Johns Hopkins University; Jaime G. Deville, University of California, Los Angeles; Eric Feucht, Branson Methodist Hospital; Judith Feinberg, University of Cincinnati; Thomas Luke, The Henry Jackson Foundation for the Advancement of Military Medicine; Kanakatte Raviprakash, Naval Medical Research Center; Janine Danko, Walter Reed National Military Medical Center; Dorothy O'Neil, Scientific Systems, Inc.; Julia A. Metcalf, National Institute of Allergy and Infectious Diseases; Karen King, Johns Hopkins University; Timothy H. Burgess, University of the Health Sciences; Evgenia Aga, Harvard School of Public Health; H. Clifford Lane, National Institute of Allergy and Infectious Diseases; Michael D. Hughes, Harvard School of Public Health; Richard T. Davey, National Institute of Allergy and Infectious Diseases
• Language: English
• Date: 2017-06-01
• Publisher: Elsevier: Lancet
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier Ltd
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/S2213-2600(17)30174-1
• Title of Journal or Parent Work: Lancet Respiratory Medicine
• ISSN: 2213-2600
• Volume: 5
• Issue: 6
• Start Page: 500
• End Page: 511
• Grant/Funding Information: The study was funded and sponsored by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, Bethesda, MD. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E.; National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States.
• Keywords: Humans; Plasma; Middle Aged; Male; Blood Component Transfusion; Case-Control Studies; Treatment Outcome; Aged; Respiration, Artificial; Influenza, Human; Kaplan-Meier Estimate; Female; Length of Stay; Adult

Abstract

Background Influenza causes substantial morbidity and mortality despite available treatments. Anecdotal reports suggest that plasma with high antibody titres to influenza might be of benefit in the treatment of severe influenza. Methods In this randomised, open-label, multicentre, phase 2 trial, 29 academic medical centres in the USA assessed the safety and efficacy of anti-influenza plasma with haemagglutination inhibition antibody titres of 1:80 or more to the infecting strain. Hospitalised children and adults (including pregnant women) with severe influenza A or B (defined as the presence of hypoxia or tachypnoea) were randomly assigned to receive either two units (or paediatric equivalent) of anti-influenza plasma plus standard care, versus standard care alone, and were followed up for 28 days. The primary endpoint was time to normalisation of patients' respiratory status (respiratory rate of ≤20 breaths per min for adults or age-defined thresholds of 20–38 breaths per min for children) and a room air oxygen saturation of 93% or more. This study is registered with ClinicalTrials.gov, number NCT01052480. Findings Between Jan 13, 2011, and March 2, 2015, 113 participants were screened for eligibility and 98 were randomly assigned from 20 out of 29 participating sites. Of the participants with confirmed influenza (by PCR), 28 (67%) of 42 in the plasma plus standard care group normalised their respiratory status by day 28 compared with 24 (53%) of 45 participants on standard care alone (p=0·069). The hazard ratio (HR) comparing plasma plus standard care with standard care alone was 1·71 (95% CI 0·96–3·06). Six participants died, one (2%) from the plasma plus standard care group and five (10%) from the standard care group (HR 0·19 [95% CI 0·02–1·65], p=0·093). Participants in the plasma plus standard care group had non-significant reductions in days in hospital (median 6 days [IQR 4–16] vs 11 days [5–25], p=0·13) and days on mechanical ventilation (median 0 days [IQR 0–6] vs 3 days [0–14], p=0·14). Fewer plasma plus standard care participants had serious adverse events compared with standard care alone recipients (nine [20%] of 46 vs 20 [38%] of 52, p=0·041), the most frequent of which were acute respiratory distress syndrome (one [2%] vs two [4%] patients) and stroke (one [2%] vs two [4%] patients). Interpretation Although there was no significant effect of plasma treatment on the primary endpoint, the treatment seemed safe and well tolerated. A phase 3 randomised trial is now underway to further assess this intervention. Funding National Institute of Allergy and Infectious Diseases, US National Institutes of Health.