The REMAP-CAP (Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community Acquired Pneumonia) is an established international, adaptive platform trial recruiting in 350 hospitals in 25 countries across 5 continents led in Ireland by the HRB-Irish Critical Care-Clinical Trials Network with 8 Irish hospitals currently engaged.
Severe community acquired pneumonia is a leading cause of death and disability worldwide (4th highest, WHO, 2019) and affects thousands of Irish patients annually. This includes patients with bacterial and viral pneumonia including influenza, and COVID-19.
We propose to examine the effectiveness of two new interventions within REMAP-CAP to reduce mortality. The first intervention is immune modulation; with either tocilizumab (a monoclonal antibody targeting IL-6) or baricitinib (a Janus Kinase 1/JAK2 inhibitor) in patients with severe CAP caused by influenza. These agents target key inflammatory and cytokine pathways (IL-6) important in severe influenza and REMAP-CAP demonstrated their effectiveness in treating COVID-19 (similar pathways involved). The second intervention is imatinib, a tyrosine kinase inhibitor, that prevents endothelial damage protecting alveoli from inflammation and oedema formation which can lead to impaired gas exchange, respiratory failure, and death. This endothelial modulation may be important in severe CAP and imatinib has shown potential in treating COVID-19. Imatinib will be evaluated in all patients with severe CAP, irrespective of the suspected pathogen. We will assess whether these strategies improve patient survival, quality of life and outcomes.
REMAP-CAP-Ireland will be the first large multicentre phase III clinical trial evaluating these promising interventions in CAP and influenza. REMAP-CAP uses novel innovative adaptive design features, Bayesian statistical methods, and has embedded trials methodology SWAT, biomarker sub-study, and health economic analysis.
We have already successfully established this platform (key results already altered clinical practice), have a network of sites in Ireland and internationally, an expert applicant team and have conducted evidence synthesis (including WHO REACT systematic reviews), developed the protocols and demonstrated intervention feasibility.
We are seeking funding to support the conduct of this study throughout Ireland in our network. If effective these interventions will improve the lives of hundreds of thousands of patients, their families and reduce costs.
