Several years ago, as an ICaR-VU (the former Institute for Cardiovascular Research of the VU University) PhD student, Jurjan Aman showed that the kinase inhibitor imatinib improves the endothelial barrier when jeopardized by inflammation. In a collaboration with Harm Jan Bogaard and his team of pulmonary vascular researchers, Aman applied his observations to clinical challenges posed by COVID-19. With a start-up grant from the Amsterdam Foundation, Aman and Bogaard designed a randomized clinical trial, the CounterCOVID study, to test the hypothesis that imatinib reduces vascular leakage in COVID-19 and thereby enables patients to recover more quickly from respiratory support (mechanical ventilation and supplemental oxygen). The trial was quickly approved by the Medical Ethics Review Committee and within a few weeks 13 hospitals had been recruited to participate in the study. Additional funding was obtained from ZonMw and the EU Innovative Medicines Initiative (IMI).
To conduct the study, a large team of young cardiovascular investigators, who were temporarily unable to perform their own research due to the Corona lockdown, was assembled. Between March 2020 and January 2021 four hundred patients were treated with imatinib or placebo. The results of the study are currently under peer review, but because of the clear indications of clinical benefit from imatinib, follow-up trials are currently being conducted and planned. These follow-up studies include a study using an intravenous imatinib formulation in the ICU (INVENT-COVID) and incorporation of imatinib as a treatment arm in the international, WHO sponsored, SOLIDARITY platform.
An extraordinary journey of translational research that has led to clinical application with the potential of a global impact.
Aman and Bogaard consider the CounterCOVID study an extraordinary journey of translational research that has led to clinical application with the potential of a global impact. Making this journey together with a group of cardiovascular researchers who were not particularly invested in clinical trials and infectious diseases made it all the more special. Now we can only hope that the use of imatinib will quickly be implemented in daily practice. It is likely that the advantages of imatinib treatment, a relatively cheap and safe drug, will probably be greatest in low-income countries with limited resources, access to vaccines and expensive immune modulators.
This article is published in June 2021 in the ACS magazine 2021, page 16.