BACKGROUND: Pseudomonas aeruginosa infections are a serious threat in intensive care units (ICUs). The aim of this confirmatory, randomized, multicenter, placebo-controlled, double-blind, phase 2/3 study was to assess the efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in non-surgical ICU patients. METHODS: Eight hundred patients aged 18 to 80 years admitted to the ICU with expected need for mechanical ventilation for ≥ 48 h were randomized 1:1 to either IC43 100 μg or saline placebo, given in two vaccinations 7 days apart. The primary efficacy endpoint was all-cause mortality in patients 28 days after the first vaccination. Immunogenicity and safety were also evaluated. FINDINGS: All-cause mortality rates at day 28 were 29.2% vs 27.7% in the IC43 and placebo groups, respectively (P = .67). Overall survival (Kaplan-Meier survival estimates, P = .46) and proportion of patients with ≥ one confirmed P. aeruginosa invasive infection or respiratory tract infection also did not differ significantly between both groups. The geometric mean fold increase in OprF/I titers was 1.5 after the first vaccination, 20 at day 28, after the second vaccination, and 2.9 at day 180. Significantly more patients in the placebo group (96.5%) had ≥ one adverse event (AE) versus the IC43 100 μg group (93.1%) (P = .04). The most frequently reported severe AEs in the IC43 and placebo groups were respiratory failure (6.9% vs 5.7%, respectively), septic shock (4.1% vs 6.5%), cardiac arrest (4.3% vs 5.7%), multiorgan failure (4.6% vs 5.5%), and sepsis (4.6% vs 4.2%). No related serious AEs were reported in the IC43 group. INTERPRETATION: The IC43 100 μg vaccine was well tolerated in this large population of medically ill, mechanically ventilated patients. The vaccine achieved high immunogenicity but provided no clinical benefit over placebo in terms of overall mortality. TRIAL REGISTRATION: https://clinicaltrials.gov (NCT01563263). Registration was sent to ClinicalTrials.gov on March 14, 2012, but posted by ClinicalTrials.gov on March 26, 2012. The first subject was included in the trial on March 22, 2012.

Assign Data Management and Biostatistics GmbH Innsbruck Austria

Centro de Investigacion Biomedica en Red Hospital Universitari Vall d'Hebron Barcelona Spain

Department of Cardiology Vienna North Hospital Clinic Floridsdorf and the Karl Landsteiner Institute for Cardiovascular and Critical Care Research Vienna Austria

Erasme University Hospital Brussels Belgium

Fakultní nemocnice U Svaté Anny v Brně Brno Czech Republic

GSK Vaccines Rockville MD USA

HELIOS Klinikum Erfurt GmbH Erfurt Germany

Hospital Universitario de Getafe CIBER de Enfermedades Respiratorias Universidad Europea Madrid Spain

Kenézy Kórház Debrecen Debrecen Hungary

Klinikum Dortmund GmbH Dortmund Germany

Medical University of Graz Graz Austria

Medical University of Vienna Vienna Austria

Országos Korányi TBC és Pulmonológiai Intézet Budapest Hungary

Szegedi Tudományegyetem Szeged Hungary

Technische Universität Dresden Dresden Germany

Universitair Ziekenhuis Brussel Brussels Belgium

Universitair Ziekenhuis Gent Ghent Belgium

University Hospital Augsburg Augsburg Germany

Valneva Austria GmbH Campus Vienna Biocenter 3 1030 Vienna Austria

Ziekenhuis Oost Limburg Campus St Jan Genk Belgium

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NCT01563263