PRACTICAL-Ireland is a harmonized Platform for international Randomized Bayesian Adaptive Clinical Trials in acute hypoxaemic respiratory failure (AHRF). AHRF affects ~5 million patients annually and commonly requires ICU admission. A severe form of AHRF called Acute Respiratory Distress Syndrome (ARDS) causes 30-50% mortality. We have identified two ARDS patient phenotypes, which differ in their immune responses (hypo-inflammatory and hyper-inflammatory) and may require different treatments. The PRACTICAL platform is active in 7 countries (additional 6 in set-up and 160 hospitals in total) with 6 Irish hospitals coordinated by the HRB-Irish Critical Care-Clinical Trials Network.
We will study two groups of interventions (called ‘domains’). 1. Invasive Mechanical Ventilation (‘IMV’) domain. AHRF patients often require IMV but there is a high risk for ventilator induced lung injury due to increased volume and pressure, leading to multi-organ failure and death. Conventional lung-protective ventilation has been the standard of care for decades. We propose to test a driving pressure-limited ventilation strategy that could be even more protective and improve outcomes. This is currently the highest recruiting PRACTICAL domain with broad inclusion for many Irish patients. 2. A Precision medicine in Hypoxaemic acutE respiratory failure (‘PANTHER’) Irish-led domain. There are no proven ARDS pharmacological treatments to date, likely because of its clinical and biological heterogeneity. We propose to assess two interventions; Simvastatin, a common cholesterol-lowering drug, and, Baricitinib an immunomodulatory rheumatoid arthritis medication. Both were effective in COVID-19 by reducing inflammation and repairing lung blood vessels. They will be tested to improve outcomes in the two inflammatory phenotypes, for a precision medicine approach, as we don’t know yet who may benefit most. We are seeking funding to conduct this study throughout Ireland as part of the first multicentre clinical trial evaluating these interventions across the AHRF spectrum, to improve the lives of countless patients and families.
