In patients with COVID-19, treatment with the tyrosine-kinase inhibitor imatinib did not reduce the time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours, but the agent did have noticeable effects on survival and duration of mechanical ventilation use in these patients. This was according to research findings published in the Lancet Respiratory Medicine.
The multicenter randomized study included patients (median age 64 years) who were hospitalized for COVID-19 across 13 hospitals in the Netherlands between March 2020 and January 2021. Patients were randomized to receive either oral imatinib (n=197) or placebo (n=188). Imatinib was administered as a loading dose of 800 mg (day 0) and then 400 mg daily (days 1 to 9). Researchers compared the 2 groups in terms of the time to discontinuation of mechanical ventilation and supplemental oxygen for more than 48 consecutive hours while alive during a 28-day period.
There was no significant difference between the 2 groups in terms of the time to discontinuation of ventilation and supplemental oxygen for more than 48 hours (unadjusted hazard ratio [HR], 0.95; 95% CI, 0.76–1.20; P =.69). A smaller proportion of patients in the imatinib group had died by day 28 (8% vs 14%, respectively; unadjusted HR, 0.51; 95% CI, 0.27–0.95), but the HRs for mortality were attenuated and differences between the groups became nonsignificant following adjustment for sex, obesity, diabetes, and cardiovascular disease (adjusted HR, 0.52; 95% CI, 0.26–1.05; P =.068).
No significant difference was found between the 2 groups in terms of the HR for the need of mechanical ventilation (adjusted HR, 1.02; 95% CI, 0.80–1.30; P =.87). The median duration of invasive mechanical ventilation was significantly shorter in the imatinib group vs the placebo group (7 days vs 12 days P =.0080). The investigators observed at least 1 adverse event (AE) of grade 3 or more in 46% of patients in the imatinib arm and 44% of patients in the placebo group. In the safety evaluation, the researchers found no evidence of imatinib-associated AEs.
The investigators noted that the 28-day duration of the study may be shorter than other COVID-19 treatment trials, which may limit the findings.
Despite this limitation, the researchers wrote that “the reduction in mortality (even if attenuated after correction for baseline imbalances) and duration of mechanical ventilation indicates that imatinib might confer clinical benefit in patients with COVID-19, and provide a rationale for further studies.”
Aman J, Duijvelaar E, Botros L, et al. Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial. Lancet Respir Med. 2021;9(9):957-968. doi:10.1016/S2213-2600(21)00237-X