Intravenous Imatinib in Mechanically Ventilated COVID-19 Patients

Summary

The SARS-CoV2 pandemic and resulting COVID-19 infection has led to a large increase in the number of patients with acute respiratory distress syndrome (ARDS). ARDS is a severe, life-threatening medical condition characterised by inflammation and fluid in the lungs. There is no proven therapy to reduce fluid leak, also known as pulmonary oedema, in ARDS. However, recent studies have discovered that imatinib strengthens the cell barrier and prevents fluid leak in the lungs in inflammatory conditions, while leaving the immune response intact. The investigators hypothesize that imatinib limits pulmonary oedema observed in ARDS due to COVID-19, and may thus help to reverse hypoxemic respiratory failure and to hasten recovery. The hypothesis will be tested by conducting a randomised, double-blind, parallel-group, placebo-controlled multi-centre clinical study of intravenous imatinib in 90 mechanically-ventilated, adult subjects with COVID-19-related ARDS. Study participants will receive the study drug (imatinib or placebo) twice daily for a period of 7 days. The effect of the intervention will be tested by measuring extravascular lung water (i.e. pulmonary oedema) difference between day 1 and day 4, using a PiCCO catheter (= pulse contour cardiac monitoring device). Other measurements will include regular blood tests to investigate the safety and the pharmacokinetic properties of imatinib, as well as biomarkers of inflammation and cellular dysfunction. Furthermore, parameters of ventilation and morbidity and mortality will be recorded as secondary outcome measures.

Timeline

Start

2021-03-14

Primary completion

2022-03-16

Completion

2022-04-07

Publications

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• Atmowihardjo LN, Schippers JR, Haaksma ME, Smit MR, Bogaard HJ, Heunks L, Juffermans NP, Schultz MJ, Endeman H, van Velzen P, Tuinman PR, Aman J, Bos LDJ. The diagnostic accuracy of lung ultrasound to determine PiCCO-derived extravascular lung water in invasively ventilated patients with COVID-19 ARDS. Ultrasound J. 2023 Oct 2;15(1):40. doi: 10.1186/s13089-023-00340-7.
• Atmowihardjo LN, Schippers JR, Duijvelaar E, Bartelink IH, Bet PM, Swart NEL, van Rein N, Purdy K, Cavalla D, McElroy A, Fritchley S, Vonk Noordegraaf A, Endeman H, van Velzen P, Koopmans M, Bogaard HJ, Heunks L, Juffermans N, Schultz MJ, Tuinman PR, Bos LDJ, Aman J. Efficacy and safety of intravenous imatinib in COVID-19 ARDS: a randomized, double-blind, placebo-controlled clinical trial. Crit Care. 2023 Jun 8;27(1):226. doi: 10.1186/s13054-023-04516-4.
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