RESUMEN
Background: A central hallmark of ARDS is hypoxemic respiratory failure due to increased pulmonary capillary leakage. The kinase inhibitor imatinib was shown to reverse vascular leak. This study aimed to investigate the effect of intravenous imatinib on pulmonary edema in patients with COVID-19 ARDS. Method(s): This multicentre, randomised, double-blind, placebo-controlled clinical trial (ClinicalTrial.gov identifier NCT04794088) included adult patients admitted to the ICU with moderate or severe COVID-19 ARDS. Patients were randomised 1:1 to receive 200mg intravenous imatinib or placebo twice daily for seven days or until ICU discharge. The change in extravascular lung water index between day 1 and day 4, measured using a PiCCO catheter, was chosen as the primary endpoint. Secondary outcomes included the PaO2/FiO2 ratio, number of ventilator free days, length of ICU admission and 28-day mortality rate. Study drug safety was assessed by daily screening of the patient records for adverse and serious adverse event occurrence and by performing ECGs and targeted clinical laboratory tests to monitor renal, liver and cardiac function. Result(s): Between March 2021 and 2022, 67 predominantly male (58%) patients with a mean age of 63+/-10 years were randomized to receive imatinib or placebo. No adverse events were considered to be related to study drug administration. At the moment of the submission, data cleaning is still ongoing. Conclusion(s): Thus far, intravenous imatinib administration seems safe and feasible in patients with COVID-19 related ARDS.
RESUMEN
Background: A high incidence of invasive mucormycosis (IM) among COVID-19 patients has been reported, especially in India. In other countries, the prevalence of IM among critically ill COVID-19 patients remains unclear. As the diagnostic utility of respiratory cultures could be low, patients may die due to undiagnosed IM. Aims and objectives: The aim was to determine the frequency of IM in invasively ventilated Covid-19 patients, who died of mono-organ respiratory failure. Method(s): Retrospectively, deceased COVID-19 ICU patients from the AmsterdamUMC with at least one BAL sample obtained in the 14 days before death were selected for this study. BAL samples were tested with a quantitative Mucor PCR assay (MucorGenius, PathoNostics, Maastricht). Result(s): Between September 2020 and April 2021, 90 patients met the inclusion criteria. The mean age was 66.7 years (SD9.01), 69 patients (76.7%) were male and 30 patients (33.3%) had a history of diabetes mellitus. The median duration of ICU admission was 18 days [13, 25.75] and the time between last BAL and death was 5.5 days [4, 7.25]. Out of 90 patients, 89 patients had a negative Mucor PCR and 1 was constrained. Conclusion(s): In our cohort of 90 deceased COVID-19 ICU patients with respiratory failure, no IM was found, indicating that IM did not contribute to the cause of death. Furthermore, it is unlikely that mucormycetes were present as a colonizer of the respiratory tract. Our results suggest that IM remains a rare disease in critically ill COVID-19 patients and is not underdiagnosed.