Journal article
Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study
01 Jun 2017
Abstract
BackgroundInfluenza 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.MethodsIn 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.FindingsBetween 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).InterpretationAlthough 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.FundingNational Institute of Allergy and Infectious Diseases, US National Institutes of Health.
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Details
- Title
- Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study
- Creators
- John H BeigelPablo TebasMarie-Carmelle Elie-TurenneEdnan BajwaTodd E BellCharles B CairnsShmuel ShohamJaime G DevilleEric FeuchtJudith FeinbergThomas LukeKanakatte RaviprakashJanine DankoDorothy O'NeilJulia A MetcalfKaren KingTimothy H BurgessEvgenia AgaH Clifford LaneMichael D HughesRichard T DaveyIRC Study TeamJoseph QuinnYan JiangRobyn HoelleNicole IovineRobert Shawn WillsSocorro PataMonique HugginsBelinda ManukianCarrie HollandKelsey BraitTaylor HuntChristopher StowellAmy SlaterMary TownsendsEugenia B QuackenbushYara A ParkPaul Gaither JordanCherie BlanchetKevin ChronowskiKathleen AlvarezDarin OstranderTerry WoessnerSandra ThomanJames LinAlyssa ZimanKavita ShankarTom BlokDon BattsBob BeckGail MasseyCarol BradleyPatricia CareyJenifer BaerEva Moore WhiteheadSharon KohrsRobert GiulittoChristina SchofieldMary FairchokSusan ChambersCindy BakerRNMichelle ParkerMarta HarshbargerM Hong NguyenMary Ellen CareyJulie ParonishFrank CornellJim CramerDiana Lynn PakstisMichael G IsonRichard WunderinkMarshall GlesbyKirsis HamValery HughesMelissa CushingCheryl GossJoanne GrenadePauline K ParkLena M NapolitanoKrishnan RaghavendranRobert C HyzyRobertson DavenportKristin BrierleyTheresa DownsMichelle Ng GongJoan UehlingerMichael LinJanice FritscheTondria Green
- Publisher
- eScholarship, University of California
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Urban Health Collaborative
- Identifiers
- 991021463607704721