ABSTRACT
Background: A central hallmark of ARDS is hypoxemic respiratory failure due to increased pulmonary capillary leakage. The kinase inhibitor imatinib was shown to reverse vascular leak. This study aimed to investigate the effect of intravenous imatinib on pulmonary edema in patients with COVID-19 ARDS. Method(s): This multicentre, randomised, double-blind, placebo-controlled clinical trial (ClinicalTrial.gov identifier NCT04794088) included adult patients admitted to the ICU with moderate or severe COVID-19 ARDS. Patients were randomised 1:1 to receive 200mg intravenous imatinib or placebo twice daily for seven days or until ICU discharge. The change in extravascular lung water index between day 1 and day 4, measured using a PiCCO catheter, was chosen as the primary endpoint. Secondary outcomes included the PaO2/FiO2 ratio, number of ventilator free days, length of ICU admission and 28-day mortality rate. Study drug safety was assessed by daily screening of the patient records for adverse and serious adverse event occurrence and by performing ECGs and targeted clinical laboratory tests to monitor renal, liver and cardiac function. Result(s): Between March 2021 and 2022, 67 predominantly male (58%) patients with a mean age of 63+/-10 years were randomized to receive imatinib or placebo. No adverse events were considered to be related to study drug administration. At the moment of the submission, data cleaning is still ongoing. Conclusion(s): Thus far, intravenous imatinib administration seems safe and feasible in patients with COVID-19 related ARDS.
ABSTRACT
Drug repurposing offers a more efficient route to medicinal innovation than conventional new molecular entity research, and proposals for repurposing projects can come from in silico algorithms, pharmacological experimentation, clinical serendipity or retrospective analysis of human data. These approaches offer a much larger number of hypotheses for validation than can be resourced, and rigorous multidisciplinary prioritisation is required. The recent COVID-19 pandemic has highlighted the potential for the approach, which has produced three clinically effective treatments in under a year, including two regulatory approvals for emergency use, and one drug with demonstrated efficacy against mortality. Challenges remain in how to provide additional commercial incentives for drug companies to support late-stage development of repurposing projects and fully realise its healthcare potential. © The Royal Society of Chemistry 2022.