A randomized placebo-controlled phase II study of a Pseudomonas vaccine in ventilated ICU patients
Rello, Jordi (Hospital Universitari Vall d'Hebron)
Krenn, Claus-Georg (Medical University of Vienna)
Locker, Gottfried (Medical University of Vienna)
Pilger, Ernst (University Hospital Graz, Graz, Austria)
Madl, Christian (Medical University of Vienna)
Balica, Laura (Emergency Clinical Hospital Bucharest)
Dugernier, Thierry (Clinique St. Pierre, Ottignies, Belgium)
Laterre, Pierre-Francois (St. Luc University Hospital UCL, Université Catholique de Louvain, Brussels, Belgium)
Spapen, Herbert (University Hospital Vrije Universiteit Brussels, Brussels, Belgium)
Depuydt, Pieter (UZ Gent, Gent, Belgium)
Vincent, Jean-Louis (Université Libre de Bruxelles)
Bogár, Lajos (University of Pécs, Pécs, Hungary)
Szabó, Zsuzsanna (Uzsoki Hospital, Budapest, Hungary)
Völgyes, Barbara (Bajcsy Zsilinszky Hospital and Polyclinic, Budapest, Hungary)
Máñez, Rafael (Hospital Universitari de Bellvitge)
Çakar, Nahit (Istanbul University Capa Medical Faculty, Istanbul, Turkey)
Ramazanoglu, Atilla (Akdeniz University, Antalya, Turkey)
Topeli, Arzu (Hacettepe University Hospital, Ankara, Turkey)
Mastruzzo, Maria A. (Hospital Dr. Carlos Bocalandro, Buenos Aires, Argentina)
Jasovich, Abel (Sanatorio Güemes, Buenos Aires, Argentina)
Remolif, Christian G. (Hospital "Heroes de Malvinas", Buenos Aires, Argentina)
del Carmen Soria, Liliana (Hospital Central Mendoza, Ciudad de Mendoza, Argentina)
Andresen Hernandez, Max A. (Pontificia Universidad Católica de Chile)
Ruiz Balart, Carolina (Hospital Dr. Sótero del Rio, Santiago, Chile)
Krémer, Ildikó (Flor Ferenc County Hospital, Kistarcsa, Hungary)
Molnár, Zsolt (University of Szeged, Szeged, Hungary)
von Sonnenburg, Frank (University of Munich, Germany)
Lyons, Arthur (Walter Reed Army Institute of Research)
Joannidis, Michael (Medical University of Innsbruck, Innsbruck, Austria)
Burgmann, Heinz (Medical University of Vienna)
Welte, Tobias (Hannover Medical School, Hannover, Germany)
Klingler, Anton (Assign Data Management and Biostatistics GmbH, Innsbruck, Austria)
Hochreiter, Romana (Valneva Austria GmbH, Campus Vienna Biocenter 3, Vienna, Austria)
Westritschnig, Kerstin (Valneva Austria GmbH, Campus Vienna Biocenter 3, Vienna, Austria)
Universitat Autònoma de Barcelona

Date:	2017
Abstract:	Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0. 0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80. 6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11. 2-14. 0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1. 9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3. 1-10. 6%) was observed in the IC43 groups. This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 μg IC43 without adjuvant compared with 200 μg IC43 with adjuvant, the 100 μg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns. ClinicalTrials. gov, . Registered on 3 April 2009. The online version of this article (doi:10. 1186/s13054-017-1601-9) contains supplementary material, which is available to authorized users.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Pseudomonas aeruginosa ; Vaccination ; Immunity ; Immunocompromised host ; Bacterial infections ; Mortality
Published in:	Critical Care, Vol. 21 (february 2017) , ISSN 1466-609X

DOI: 10.1186/s13054-017-1601-9
PMID: 28159015

13 p, 786.1 KB

The record appears in these collections:
Articles > Research articles
Articles > Published articles