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Background Oncohematological patients, due to their secondary immunodeficiency, are at a higher risk of mortality related to COVID-19 infection. Baricitinib, a JAK2 inhibitor, has a dual effect in this context, reducing the inflammatory response to the virus and diminishing virus endocytosis. Methods This phase I safety run-in cohort study aimed to determine the dose-limiting toxicity of baricitinib in terms of the rate of serious events in oncohematological patients with COVID-19. The drug was administered on an inpatient basis at an oral dose of 4 mg daily for 5 to 7 days, associated with the institutional standard of care (SOC). Results Six patients with solid tumors or hematological malignancies were enrolled in the study. Sixty percent of the patients received active anticancer treatment at the time of inclusion. Lymphopenia and elevation of acute-phase reactants were the most frequent laboratory findings that improved during the treatment course. All patients received corticosteroids, but only 3 of them received remdesivir as the SOC. The most common adverse events were bacterial infections, including pneumonia, urinary tract infections, and bacteremia. The mortality rate due to disease progression and respiratory insufficiency is 33%. The severe adverse event rate was less than 33%, with no adverse events or mortality caused by baricitinib. Conclusions The results of the present study demonstrate that baricitinib is a safe treatment for patients with oncohematological diseases and COVID-19. However, its efficacy and superiority to standard treatment will require further testing in phases 2 and 3 trials. Trial registration: AEMPs: 20–0356 EudraCT: 2020-001789-12

Background Febrile neutropenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal β-lactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. However, the clinical efficacy of BLA may be diminished in these patients because they present with pathophysiological variations that compromise the pharmacokinetic (PK) parameters of these antibiotics. Optimized administration of BLA in prolonged infusions has demonstrated better clinical outcomes in critically ill patients. However, there is a paucity of data on the usefulness of this strategy in patients with FN. The aim of this study is to test the hypothesis that the administration of BLA would be clinically more effective by extended infusion (EI) than by intermittent infusion (II) in haematologic patients with FN.Methods A randomised, multicentre, open-label, superiority clinical trial will be performed. Patients with haematological malignancies undergoing chemotherapy or haematopoietic stem cell transplant and who have FN and receive empirical antibiotic therapy with cefepime, piperacillin-tazobactam or meropenem will be randomised (1:1) to receive the antibiotic by EI (during half the time of the dosing interval) in the study group, or by II (30 minutes) in the control group. The primary endpoint will be clinical efficacy, defined as defervescence without modifying the antibiotic treatment administered within the first 5 days of therapy. The primary endpoint will be analysed in the intention-to-treat population. The secondary endpoints will be pharmacokinetic/pharmacodynamic (PK/PD) target achievement, bacteraemia clearance, decrease in C-reactive protein, overall (30-day) case-fatality rate, adverse events and development of a population PK model of the BLA studied.Discussion Data on the usefulness of BLA administration in patients with FN are scant. Only three clinical studies addressing this issue have been published thus far, with contradictory results. Moreover, these studies had some methodological flaws that limit the interpretation of their findings. If this randomised, multicentre, phase IV, open-label, superiority clinical trial validates the hypothesis that the administration of BLA is clinically more effective by EI than by II in haematologic patients with FN, then the daily routine management of these high-risk patients could be changed to improve their outcomes.Trial registration: European Clinical Trials Database: EudraCT 2018-001476-37ClinicalTrials.gov Identifier: NCT04233996