ABSTRACT
Background: COVID-19 has quickly become a global pandemic with a substantial number of deaths and a substantial burden for healthcare systems worldwide. Although most cases are paucisymptomatic and limited to the viral infection related symptoms, some patients evolve to a second phase, with an impaired inflammatory response (cytokine storm) that may lead to acute respiratory distress syndrome and death. This is thought to be caused by an increased bradykinin synthesis. Methods: : ICAT-COVID is a multicenter, randomized, open-label, proof-of-concept phase II clinical trial assessing the clinical efficacy and safety of adding Icatibant on the standard of care in patients hospitalized with COVID-19 without invasive mechanical ventilation. Patients hospitalized with a confirmed COVID-19 pneumonia diagnosis (RT-PCR or antigen test ≤ 10 days prior to randomization, and radiographic evidence of pulmonary infiltrates), rated ‘4’ or ‘5’ on the WHO’s clinical status scale are eligible. Patients will be randomized on a 1:1 ratio to either standard of care-plus-Icatibant (experimental group) or to standard of care alone (control group). The experimental group will receive 30 mg of Icatibant subcutaneously 3 times a day for 3 days (for a total of 9 doses). The expected sample size is of 120 patients (60 per group) gathered from 2 centers in Spain. Primary outcomes are Icatibant’s efficacy and safety. The main efficacy outcome is the number of patients reaching grades ‘2’ or ‘1’ on the WHO Scale within 10 days of treatment start. Among the secondary outcomes are ‘long-term efficacy’: number of patients discharged who do not present any COVID-19-related relapse or comorbidity up until 28 days after discharging, and mortality. Discussion: Icatibant, a bradykinin type 2 receptor antagonist with proven effectiveness and safety against hereditary angioedema attacks, may be beneficial for COVID-19 patients by inhibiting bradykinin’s action on endothelial cells and by inhibiting the SARS-CoV-2 M protease. Our working hypothesis is that treatment with Standard of Care-plus-Icatibant is effective and safe to treat patients infected with SARS-CoV-2 admitted to hospital for pneumonia without invasive mechanical ventilation. Trial registration: EudraCT: 2020-002166-13; ClinicalTrials.gov: NCT04978051