Final results of an adaptive randomized open-label controlled study on the efficacy and safety of enisamium iodide for inpatient treatment of the COVID-19 infection
Authors:   Central Research Institute of Epidemiology, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Moscow, Russian Federation, Pshenichnaya N.Yu. ,   M.F.Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russian Federation, Zhdanov K.V. ,   S.M.Kirov Military Medical Academy, Saint Petersburg, Russian Federation, Lioznov D.A. ,   Smorodintsev Research Institute of Influenza, Saint Petersburg, Russian Federation,   Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russian Federation
Published: March 2024

Despite extensive vaccination as well as the introduction of new therapies for COVID-19, morbidity and mortality rates remain high worldwide, especially among the unvaccinated population and patients at risk. One possible strategy for improving the treatment of patients with COVID-19 could be to study the efficacy and safety of existing antiviral or immunomodulatory agents against SARS-CoV-2 and their impact on the course of the disease. Objective. To assess the efficacy and safety of enisamium iodide – Nobazit®, film-coated tablets, 250 mg (Avexima LLC, Russian Federation), for inpatient treatment of moderate coronavirus disease caused by the SARS-CoV-2 (COVID-19). Patients and methods. This was an open-label, multicentre, randomized study that enrolled 304 hospitalized patients with moderate COVID-19. Patients were divided into 2 groups: the enisamium iodide group (n = 151) included patients who received therapy according to the current version of the Interim Guidelines “Prevention, Diagnosis and Treatment of New Coronavirus Infection (COVID-19)” (IG) except for etiotropic drugs in combination with enisamium iodide (500 mg 3 times daily for 7 days); the routine therapy group (n = 153) included patients who received therapy according to IG, including etiotropic drugs. The primary efficacy endpoint (first component) was a composite of the median time (in days) from the initiation of treatment with study drug/routine therapy to sustained resolution of fever, reduction in respiratory rate to less than 22/min, and achievement of blood oxygen saturation (SpO2) more than 96%. The second component of the primary endpoint was the proportion of patients who developed respiratory failure. Secondary endpoints included all-cause mortality, duration of hospitalization, change in World Health Organization (WHO) 8-point scale score, median time to reduction in the severity of major symptoms (fever, cough, headache, myalgia, weakness). Efficacy endpoints were analysed in the intention-to-treat (ITT) and per protocol (PP) populations. Results. As follows from the analysis of the first component of the primary endpoint, the mean number of days from treatment initiation to sustained resolution of fever, normalization of the respiratory rate, and achievement of SpO2 was 8.8 in the enisamium iodide group and 10.6 in the control group (hazard ratio [HR] 0.738, p = 0.013 [97.62% CI: 0.581–0.937]). The proportion of patients who developed respiratory failure in both groups was comparable, indicating that enisamium iodide therapy does not lead to an increased risk of respiratory failure in patients with COVID-19. As for the secondary efficacy endpoints, no statistically significant differences between the groups were shown, except for the WHO 8-point scale score on days 14 and 28 in favour of the study drug (p = 0.024 and p = 0.042, respectively). In addition, there was a trend towards lower mortality in the study drug group than in the control group: 1 and 5 cases, respectively. The addition of enisamium iodide to standard therapy was not associated with a worsening in the treatment safety profile. Conclusion. The statistically significant superiority of the efficacy of adding Nobazit®, film-coated tablets, 250 mg (Avexima LLC, Russian Federation), to routine therapy over routine therapy alone in patients with moderate COVID-19 was proved. Consequently, it is reasonable to recommend the addition of Nobazit® to the standard treatment of patients with COVID-19 of moderate severity. Key words: enisamium iodide, antivirals, etiopathogenetic therapy, SARS-CoV-2, COVID-19, viral-induced lung damage, pneumonia, randomized controlled study, adaptive study, open-label study