WP1 setting up the project governance structure and procedures
WP2 Promoting and completing the first clinical trial (PREV-HAP): 109 patients have been included and the dataset has been analysed, the manuscript has been published in an international journal. The protocol of the second clinical trial (HAP-DEX trial) has been submitted to the European Agency for authorisation, first patients have been included since May 2024, and new centres in Spain, Greece and Belgium will be opened soon.
WP3 investigating HAP-specific signatures likely to influence susceptibility and severity of the disease (based on pre-existing respiratory fluids, PBMCs and plasma samples of patients from intensive care units and healthy controls) in both a pre-existing biobank and samples collected during the PREV-HAP study. During this trial, we defined a cluster of patients whose inflammatory response to IFN-g was specific and related to respiratory complications. We defined and validated a respiratory microbiome signature associated with HAP and patient unfavourable outcomes. We identified heterogeneity in the metabolomic response to critical illness related to the risk of severe HAP and a favourable response to IFN-gamma treatment.
WP4 combining pre-existing clinical data and the first “omics” data generated from WP3 to identify attributes of high predictive values. We have developed a multi-omic score for predicting HAP (early vs late and severe vs non-severe) and are in the process of external validation in the PREV-HAP cohort. We also identified groups of bacteria associated with specific immune responses and risk of HAP. Finally, we defined a clinico-biological score in HAP patients, associated with the respiratory microbiome composition, the blood cytokine landscape and the risk of treatment failure. We also found that this score can help adapt antimicrobial treatment in HAP patients
WP5 designing the methodological developments (psychometric and economic models) required to investigate the suitability, acceptability and adaptability of host-targeted treatment for HAP treatment and prevention in different population groups. We have validated this approach in the PREV-HAP cohort and demonstrated the importance of the responder in estimating the quality of life. We also demonstrated that immune therapy with IFN gamma-1b in critically ill patients is cost-effective with a 90-day perspective.
WP6 developing the project’s core dissemination and communication tools and setting up a data management strategy and data sharing infrastructure.
WP7 managing the 'ethics requirements' compliance. Based on safety regular monitoring, the PREV-HAP study was early discontinued to guarantee patient safety. We revised the benefit/risk ratio of the TREAT-HAP trial and revised the protocol based on meetings with DSMB and French regulatory agency.
