Efficacy and safety of intravenous imatinib in COVID-19 ARDS: a randomized, double-blind, placebo-controlled clinical trial
Issued Date
2023-12-01
Resource Type
ISSN
13648535
eISSN
1466609X
Scopus ID
2-s2.0-85161412002
Journal Title
Critical Care
Volume
27
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Critical Care Vol.27 No.1 (2023)
Suggested Citation
Atmowihardjo L.N., Schippers J.R., Duijvelaar E., Bartelink I.H., Bet P.M., Swart N.E.L., van Rein N., Purdy K., Cavalla D., McElroy A., Fritchley S., Vonk Noordegraaf A., Endeman H., van Velzen P., Koopmans M., Bogaard H.J., Heunks L., Juffermans N., Schultz M.J., Tuinman P.R., Bos L.D.J., Aman J. Efficacy and safety of intravenous imatinib in COVID-19 ARDS: a randomized, double-blind, placebo-controlled clinical trial. Critical Care Vol.27 No.1 (2023). doi:10.1186/s13054-023-04516-4 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/85126
Title
Efficacy and safety of intravenous imatinib in COVID-19 ARDS: a randomized, double-blind, placebo-controlled clinical trial
Author's Affiliation
Mahidol Oxford Tropical Medicine Research Unit
Hamilton Medical AG
Erasmus MC
OLVG
Erasmus Universiteit Rotterdam
Leids Universitair Medisch Centrum
Nuffield Department of Medicine
Vrije Universiteit Amsterdam
Universiteit van Amsterdam
Amsterdam UMC - University of Amsterdam
Dijklander Hospital
Exvastat Ltd.
Hamilton Medical AG
Erasmus MC
OLVG
Erasmus Universiteit Rotterdam
Leids Universitair Medisch Centrum
Nuffield Department of Medicine
Vrije Universiteit Amsterdam
Universiteit van Amsterdam
Amsterdam UMC - University of Amsterdam
Dijklander Hospital
Exvastat Ltd.
Other Contributor(s)
Abstract
Purpose: A hallmark of acute respiratory distress syndrome (ARDS) is hypoxaemic respiratory failure due to pulmonary vascular hyperpermeability. The tyrosine kinase inhibitor imatinib reversed pulmonary capillary leak in preclinical studies and improved 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 200 mg 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 subphenotypes. Results: 66 patients were randomized to imatinib (n = 33) or placebo (n = 33). There was no difference in ∆EVLWi between the groups (0.19 ml/kg, 95% CI − 3.16 to 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 (− 1.17 ml/kg, 95% CI − 1.87 to − 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. Trial registration NCT04794088 , registered 11 March 2021. European Clinical Trials Database (EudraCT number: 2020-005447-23).