Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients—a randomized clinical trial
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 a...
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Critical Care |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13054-020-2792-z |
| _version_ | 1818528774671564800 |
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| author | Christopher Adlbrecht Raphael Wurm Pieter Depuydt Herbert Spapen Jose A. Lorente Thomas Staudinger Jacques Creteur Christian Zauner Andreas Meier-Hellmann Philipp Eller Margot Vander Laenen Zsolt Molnár István Várkonyi Bernhard Schaaf Mária Héjja Vladimír Šrámek Hauke Schneider Niranjan Kanesa-thasan Susanne Eder-Lingelbach Anton Klingler Katrin Dubischar Nina Wressnigg Jordi Rello |
| author_facet | Christopher Adlbrecht Raphael Wurm Pieter Depuydt Herbert Spapen Jose A. Lorente Thomas Staudinger Jacques Creteur Christian Zauner Andreas Meier-Hellmann Philipp Eller Margot Vander Laenen Zsolt Molnár István Várkonyi Bernhard Schaaf Mária Héjja Vladimír Šrámek Hauke Schneider Niranjan Kanesa-thasan Susanne Eder-Lingelbach Anton Klingler Katrin Dubischar Nina Wressnigg Jordi Rello |
| author_sort | Christopher Adlbrecht |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T06:54:23Z |
| format | Article |
| id | doaj.art-58fdcb99ef594658b60807f8d9e0d7eb |
| institution | Directory Open Access Journal |
| issn | 1364-8535 |
| language | English |
| last_indexed | 2024-12-11T06:54:23Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Critical Care |
| spelling | doaj.art-58fdcb99ef594658b60807f8d9e0d7eb2022-12-22T01:16:49ZengBMCCritical Care1364-85352020-03-0124111010.1186/s13054-020-2792-zEfficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients—a randomized clinical trialChristopher Adlbrecht0Raphael Wurm1Pieter Depuydt2Herbert Spapen3Jose A. Lorente4Thomas Staudinger5Jacques Creteur6Christian Zauner7Andreas Meier-Hellmann8Philipp Eller9Margot Vander Laenen10Zsolt Molnár11István Várkonyi12Bernhard Schaaf13Mária Héjja14Vladimír Šrámek15Hauke Schneider16Niranjan Kanesa-thasan17Susanne Eder-Lingelbach18Anton Klingler19Katrin Dubischar20Nina Wressnigg21Jordi Rello22Department of Cardiology, Vienna North Hospital–Clinic Floridsdorf and the Karl Landsteiner Institute for Cardiovascular and Critical Care ResearchMedical University of ViennaUniversitair Ziekenhuis GentUniversitair Ziekenhuis BrusselHospital Universitario de Getafe, CIBER de Enfermedades Respiratorias, Universidad EuropeaMedical University of ViennaErasme University HospitalMedical University of ViennaHELIOS Klinikum Erfurt GmbHMedical University of GrazZiekenhuis Oost-LimburgSzegedi TudományegyetemKenézy Kórház DebrecenKlinikum Dortmund GmbHOrszágos Korányi TBC és Pulmonológiai IntézetFakultní nemocnice U Svaté Anny v BrněTechnische Universität DresdenGSK VaccinesValneva Austria GmbHAssign Data Management and Biostatistics GmbHValneva Austria GmbHValneva Austria GmbHCentro de Investigacion Biomedica en Red (CIBERES), Hospital Universitari Vall d’HebronAbstract 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.http://link.springer.com/article/10.1186/s13054-020-2792-zPseudomonas aeruginosaVaccinationIntensive careMechanical ventilation |
| spellingShingle | Christopher Adlbrecht Raphael Wurm Pieter Depuydt Herbert Spapen Jose A. Lorente Thomas Staudinger Jacques Creteur Christian Zauner Andreas Meier-Hellmann Philipp Eller Margot Vander Laenen Zsolt Molnár István Várkonyi Bernhard Schaaf Mária Héjja Vladimír Šrámek Hauke Schneider Niranjan Kanesa-thasan Susanne Eder-Lingelbach Anton Klingler Katrin Dubischar Nina Wressnigg Jordi Rello Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients—a randomized clinical trial Critical Care Pseudomonas aeruginosa Vaccination Intensive care Mechanical ventilation |
| title | Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients—a randomized clinical trial |
| title_full | Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients—a randomized clinical trial |
| title_fullStr | Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients—a randomized clinical trial |
| title_full_unstemmed | Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients—a randomized clinical trial |
| title_short | Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients—a randomized clinical trial |
| title_sort | efficacy immunogenicity and safety of ic43 recombinant pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients a randomized clinical trial |
| topic | Pseudomonas aeruginosa Vaccination Intensive care Mechanical ventilation |
| url | http://link.springer.com/article/10.1186/s13054-020-2792-z |
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