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Lancet Infect Dis. 2013 Jun;13(6):485-96. doi: 10.1016/S1473-3099(13)70046-X. Epub 2013 Mar 19.

AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial.

Collaborators (233)

Arnould PH, Balthazar Y, Batens AH, Coppens H, De Meulemeester M, De Witte P, Devriendt L, Henry G, Leroux-Roels G, Mathot G, Maury O, Muylaert P, Renson A, Soetaert P, Tilley L, Van Riet D, Bemden SV, Aggarwal N, Blouin F, Ferguson M, Gauthier JS, Lasko B, McElhaney J, McNeil S, Powell C, Rheault P, Shu D, St-Amour E, Beran J, Chocensky V, Koort I, Maasalu K, Poder A, Randvee L, Rosenthal S, Stern M, Talli J, Arnou R, Bortolotti C, Boyes JP, Dubray C, Duval X, Ferrier R, Fivel C, Foucault JF, Galtier F, Igigabel P, Launay O, Saillard D, Scellier C, Tondut J, Uge P, Beck E, Benedix A, Bergtholdt B, Burkhardt F, Colberg A, Dahmen A, Deckelmann R, Dietrich H, Dominicus R, Drescher T, Eckermann T, Elefant U, Esen M, Fahron G, Fischer S, Foerster K, Folesky H, Frick M, Gehling U, Golygowski M, Grigat C, Himpel-Boenninghoff A, Hoeschele P, Höltz S, Huber B, Ilg S, Illies G, Jansen JP, Kaessner F, Kieninger D, Klein C, Kleinecke-Pohl U, Kluge A, Kratschmann W, Krause KH, Kropp J, Langenbrink A, Lehmann R, Linnhoff A, Markendorf A, Maxeiner S, Meissner G, Meyer I, Moeckesch B, Mueller M, Mueller S, Neumann G, Paschen C, Plassmann G, Ponitz HH, Preusche A, Rinke A, Samer H, Schaberg T, Schaper F, Schenkenberger I, Schmidt J, Schmitt B, Schneider H, Schumacher M, Schwarz T, Stahl HD, Steinbach K, Steinhauser U, Stockhausen J, Stolz B, Toursarkissian N, Tyler K, Wachter J, Weber HG, Weyland K, Wolf D, Zitzmann K, Doniz CA, Guerrero ML, Lazcano-Ponce E, de Los Santos AM, Pavia-Ruz N, Ruiz-Palacios GM, van Essen GA, Richardus JH, Rumke H, Elle S, Holmberg A, Høivik HO, Kjærnli T, Norheim P, Tandberg A, Gadzinski W, Holda J, Jazwinska-Tarnawska E, Lepich T, Lysek R, Nowakowska H, Orzechowska M, Szumlanska Z, Abaitancei A, Oproiu C, Orban S, Vasilache F, Toma D, Osipova I, Perminova O, Romanenko V, Semerikov V, Hwang SJ, Yang PC, Abdulhakim E, Pavel-Knox I, Raja A, Shaw H, Blatter M, Boos D, Bowling B, Bowman S, Brune D, Christensen S, Christensen T, Civitarese L, Downey HJ, Durrence H, El Sahly H, Earl J, Ervin J, Essink B, Falsey AR, Feldman G, Fiel T, Fogarty C, Folkerth S, Frey SE, Fried D, Gibson G, Hall M, Harper W, Hull S, Jacobson J, Jacqmein J, Lawless J, Lucasti C, Middleton R, Plunkett S, Poling T, Raad G, Ramsbottom G, Reisinger K, Riffer E, Rosen J, Ross E, Rubino J, Sperber S, Studdard H, Thrasher J, Turner M, Van Cleeff M, Wadsworth L, Yakish J, Caplanusi A, Claeys C, Devaster JM, Innis B, Kovac M, Oostvogels L, Van Der Zee C, Allard F, Durviaux S, Houard N, Ollinger T, Walravens K, Dewé W, Durand C, El Idrissi M, Oujaa M, Claassen J, Grau A, Konior R, Verheugt F, Betancourt-Cravioto M, Fleming D, Nichol K, Paget WJ.

Author information

1
Health Sciences North and Advanced Medical Research Institute of Canada, Sudbury, ON, Canada.

Abstract

BACKGROUND:

We aimed to compare AS03-adjuvanted inactivated trivalent influenza vaccine (TIV) with non-adjuvanted TIV for seasonal influenza prevention in elderly people.

METHODS:

We did a randomised trial in 15 countries worldwide during the 2008-09 (year 1) and 2009-10 (year 2) influenza seasons. Eligible participants aged at least 65 years who were not in hospital or bedridden and were without acute illness were randomly assigned (1:1) to receive either AS03-adjuvanted TIV or non-adjuvanted TIV. Randomisation was done in an internet-based system, with a blocking scheme and stratification by age (65-74 years and 75 years or older). Participants were scheduled to receive one vaccine in each year, and remained in the same group in years 1 and 2. Unmasked personnel prepared and gave the vaccines, but participants and individuals assessing any study endpoint were masked. The coprimary objectives were to assess the relative efficacy of the vaccines and lot-to-lot consistency of the AS03-adjuvanted TIV (to be reported elsewhere). For the first objective, the primary endpoint was relative efficacy of the vaccines for prevention of influenza A (excluding A H1N1 pdm09) or B, or both, that was confirmed by PCR analysis in year 1 (lower limit of two-sided 95% CI had to be greater than zero to establish superiority). From Nov 15, to April 30, in both years, participants were monitored by telephone or site contact and home visits every week or 2 weeks to identify cases of influenza-like illness. After onset of suspected cases, we obtained nasal and throat swabs to identify influenza RNA with real-time PCR. Efficacy analyses were done per protocol. This trial is registered with ClinicalTrials.gov, number NCT00753272.

FINDINGS:

We enrolled 43 802 participants, of whom 21 893 were assigned to and received the AS03-adjuvanted TIV and 21 802 the non-adjuvanted TIV in year 1. In the year 1 efficacy cohort, fewer participants given AS03-adjuvanted than non-adjuvanted TIV were infected with influenza A or B, or both (274 [1·27%, 95% CI 1·12-1·43] of 21 573 vs 310 [1·44%, 1·29-1·61] of 21 482; relative efficacy 12·11%, 95% CI -3·40 to 25·29; superiority not established). Fewer participants in the year 1 efficacy cohort given AS03-adjuvanted TIV than non-adjuvanted TIV were infected with influenza A (224 [1·04%, 95% CI 0·91-1·18] vs 270 [1·26, 1·11-1·41]; relative efficacy 17·53%, 95% CI 1·55-30·92) and influenza A H3N2 (170 [0·79, 0·67-0·92] vs 205 [0·95, 0·83-1·09]; post-hoc analysis relative efficacy 22·0%, 95% CI 5·68-35·49).

INTERPRETATION:

AS03-adjuvanted TIV has a higher efficacy for prevention of some subtypes of influenza than does a non-adjuvanted TIV. Future influenza vaccine studies in elderly people should be based on subtype or lineage-specific endpoints.

FUNDING:

GlaxoSmithKline Biologicals SA.

Comment in

PMID:
23518156
DOI:
10.1016/S1473-3099(13)70046-X
[Indexed for MEDLINE]
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