Countering Lung Damage in COVID-19 infection (CounterCovid) study

Rationale: Covid19 infection is characterized by hypoxemic respiratory failure, caused by extensive vascular leak and pulmonary edema early in the course of disease. Although there is no proven therapy to reduce viral replication in Covid19, recent studies from our department have discovered that the tyrosine kinase inhibitor imatinib reinforces the endothelial barrier and prevents vascular leak in inflammatory conditions, while leaving the immune response intact. We hypothesize that reversing vascular leak is an effective approach to reduce disease burden and consumption of medical resources.
Objective: To test whether treatment with oral imatinib reduce disease burden and consumption of medical resources.
Study design: A randomized, double-blind, placebo controlled, clinical trial.
Study population: Patients (>18years) with proven Covid19 infection, admitted to the hospital with hypoxemic respiratory failure (SaO2<92% or kPa<8 on room air), with a study population of 386 patients (193/arm).
Intervention (if applicable): The intervention group will receive a starting dose of 800mg oral imatinib, followed by 400mg od during 10 days. The control group will receive a similar dosing schedule with a placebo.
Main study parameters/endpoints: The main study parameter is the time to liberation from ventilation and supplemental oxygen and alive during a 28day period after randomization.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participation involves randomization to either the intervention or the placebo group. In both groups patients will undergo blood sampling at 9 time-points, at each time-point 1 or 4 tubes of 5mL will be drawn. Additional tests include a viral swab from the throat at 2 time-points, and an ECG at 5 time-points. Part of these interventions are part of routine care. Physical discomfort associated with participation involves swallowing of tablets, and side effects of the study medication, which are considered mild (predominantly gastro-intestinal discomfort). Anticipated benefits from the study medication involve faster recovery from Covid19 and a lower risk for ICU admission or death.

Our hypothesis is that treatment with imatinib results in a reduction of the time to liberation from ventilation and supplemental oxygen and alive in Covid19.

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Imatinib or placebo