Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Mar 4;24(1):74.
doi: 10.1186/s13054-020-2792-z.

Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients-a randomized clinical trial

Christopher Adlbrecht  1 , Raphael Wurm  2 , Pieter Depuydt  3 , Herbert Spapen  4 , Jose A Lorente  5 , Thomas Staudinger  2 , Jacques Creteur  6 , Christian Zauner  2 , Andreas Meier-Hellmann  7 , Philipp Eller  8 , Margot Vander Laenen  9 , Zsolt Molnár  10 , István Várkonyi  11 , Bernhard Schaaf  12 , Mária Héjja  13 , Vladimír Šrámek  14 , Hauke Schneider  15   16 , Niranjan Kanesa-Thasan  17 , Susanne Eder-Lingelbach  18 , Anton Klingler  19 , Katrin Dubischar  18 , Nina Wressnigg  20 , Jordi Rello  21
Affiliations
Randomized Controlled Trial

Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients-a randomized clinical trial

Christopher Adlbrecht et al. Crit Care. .

Abstract

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.

Keywords: Intensive care; Mechanical ventilation; Pseudomonas aeruginosa; Vaccination.

PubMed Disclaimer

Conflict of interest statement

SE, KD, and NW are Valneva employees and own stock and share options in Valneva. NK was an employee of GSK during the study and now serves as a consultant to Valneva. JR and CA have received honorary as consultants for the sponsor. CA, RW, PD, HS, JAL, TS, JC, CZ, AMH, PE, MVL, ZM, IV, BS, MH, VŠ, HS and JR received research funding for the trial from the sponsor.

Figures

Fig. 1
Fig. 1
CONSORT diagram
Fig. 2
Fig. 2
All-cause mortality (intent-to-treat population). aIC43 100 μg versus placebo
Fig. 3
Fig. 3
Overall survival: Kaplan-Meier curves by treatment group (intent-to-treat population). Arrows depict vaccination time points. Numbers reflect a number of subjects at risk. + Symbols denote censored patients
See this image and copyright information in PMC

References

    1. Ewans T. Prevention and control of nosocomial infection in the intensive care unit. 4. New York: Lippincot-Ravan; Irwin and Rippe’s intensive care medicine - NLM Catalog - NCBI; 1999.
    1. Saviteer SM, Samsa GP, Rutala WA. Nosocomial infections in the elderly. Increased risk per hospital day. Am J Med. 1988;84:661–666. doi: 10.1016/0002-9343(88)90101-5. - DOI - PubMed
    1. Sadikot RT, Blackwell TS, Christman JW, Prince AS. Pathogen–host interactions in Pseudomonas aeruginosa pneumonia. Am J Respir Crit Care Med. 2005;171:1209–1223. doi: 10.1164/rccm.200408-1044SO. - DOI - PMC - PubMed
    1. Yum H-K, Park I-N, Shin B-M, Choi S-J. Recurrent Pseudomonas aeruginosa infection in chronic lung diseases: relapse or reinfection? Tuberc Respir Dis (Seoul) 2014;77:172. doi: 10.4046/trd.2014.77.4.172. - DOI - PMC - PubMed
    1. Morrison Allan J., Wenzel Richard P. Epidemiology of Infections Due to Pseudomonas aeruginosa. Clinical Infectious Diseases. 1984;6(Supplement_3):S627–S642. doi: 10.1093/clinids/6.Supplement_3.S627. - DOI - PubMed

Publication types

MeSH terms

Associated data