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The COVID-19 pandemic has an unprecedented impact on global health, carrying a high burden for the individual patient and at society level. An important driver of this burden is hypoxemic respiratory failure (described as ‘severe’ COVID19), resulting from damage to the alveolocapillary barrier, excessive vascular leakage and pulmonary edema. Current management is supportive, and there is still no direct therapy available to treat severe Covid19.

In the last decade we and other groups have shown that the clinically available Abl kinase inhibitor imatinib protects vascular integrity and can be used to treat vascular leak and pulmonary edema. Of note, imatinib was also shown to have antiviral properties, among others in SARS and MERS. Based on these properties we hypothesize that imatinib can reduce disease burden and health resource consumption in patients with severe Covid19.

To test this hypothesis we initiated a randomized, placebo-controlled clinical trial to test a 10-day course of oral imatinib in patients with severe Covid19, aiming to reduce the need for oxygen and ventilatory support. This trial has obtained IRB approval and has thus far included >80patients in 10 centers in the Netherlands, thereby being one of the largest investigator-driven Covid19 intervention studies in the Netherlands.

With the current proposal we aim to further increase the network of participating centers to 20 centers, to sustain the inclusion rate and finish the trial end 2020. As national referral center for pulmonary vascular disease, we will use an established large network of referring non-academic hospitals to realize this. If proven effective in this trial, it can be integrated swiftly in Covid19 management, also in low-income countries given the fact that oral imatinib is generically available. Future perspectives include application of imatinib beyond Covid19, for other diseases characterized by pulmonary vascular leak.

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