A randomised, double-blind, placebo-controlled study to investigate the safety and efficacy of intravenous imatinib mesylate (Impentri®) in subjects with Acute Respiratory Distress Syndrome (ARDS) induced by COVID-19

Purpose: A hallmark of acute respiratory distress syndrome (ARDS) is hypoxaemic respiratory failure due to pulmonary vascular hyperpermeability. The kinase inhibitor imatinib was shown to reverse pulmonary capillary leak and improve clinical outcomes in hospitalized COVID-19 patients. We investigated the effect of intravenous (IV) imatinib on pulmonary edema in COVID-19 ARDS. Methods: This was a multicenter, randomized, double-blind, placebo-controlled trial. Invasively ventilated patients with moderate-to-severe COVID-19 ARDS were randomized to 200mg IV imatinib or placebo twice daily for a maximum of seven days. The primary outcome was the change in extravascular lung water index (∆EVLWi) between days 1 and 4. Secondary outcomes included safety, duration of invasive ventilation, ventilator-free days (VFD) and 28-day mortality. Posthoc analyses were performed in previously identified biological subgroups. Results: 66 patients were randomized to imatinib (n=33) or placebo (n=33). There was no difference in ∆EVLWi between the groups (0.19ml/kg, 95% CI: -3.16–2.77, p=0.89). Imatinib treatment did not affect duration of invasive ventilation (p=0.29), VFD (p=0.29) or 28-day mortality (p=0.79). IV imatinib was well-tolerated and appeared safe. In a subgroup of patients characterized by high IL-6, TNFR1 and SP-D levels (n=20), imatinib significantly decreased EVLWi per treatment day (-1.17ml/kg, 95% CI: -1.87–(-0.44)). Conclusions: IV imatinib did not reduce pulmonary edema or improve clinical outcomes in invasively ventilated COVID-19 patients. While this trial does not support the use of imatinib in the general COVID-19 ARDS population, imatinib reduced pulmonary edema in a subgroup of patients, underscoring the potential value of predictive enrichment in ARDS trials