Стратегия управления вирус-индуцированным воспалением при COVID-19. Результаты многоцентрового адаптивного рандомизированного двойного слепого плацебо-контролируемого исследования у амбулаторных пациентов

Abstract

SARS-CoV-2 infection is associated with increased production of pro-inflammatory cytokines and chemokines, followed by the development of immunothrombosis and hypercoagulation, which are important determinants of illness severity, survival prediction and long-term post-infection sequelae. More than that, thrombotic events may even develop in non-severe COVID-19 cases, including following specific thromboprophylaxis administered concurrently with the infection treatment. Therefore, preventing excess inflammation as a cause of subsequent micro- and macro-vascular thrombotic disease is becoming an increasingly important issue today. The objective of the multi-center, adaptive, randomized, double-blind, placebo-controlled trial was to evaluate the efficacy and safety of Aterixen® (ХС221GI) in patients with mild COVID-19. Patients and methods. A total of 274 subjects (age range, 18 to 75 years) with mild COVID-19 were enrolled. The study included 3 stages: screening, drug administration, and follow-up activities. The maximum overall duration of subject participation was 32 days. The subjects were randomized into 2 similar groups receiving Aterixen® (100 mg tablets administered at a dose of 1 tablet twice daily for a total of 14 days) or placebo matching the study drug in addition to the standard treatment in line with the Temporary Guidelines of the Russian Ministry of Health for the prevention, diagnosis and treatment of COVID-19. Results. The ITT and PP efficacy analyses based on the composite primary endpoint showed that Aterixen® was superior to the placebo and had a favorable safety profile. Furthermore, the number of pneumonia cases was nearly 80% lower in Ateriхen® treated subjects who required admission to hospital. Key words: COVID-19, new coronavirus infection, cytokine hyperproduction, immunothrombosis, preventive anti-inflammatory therapy, Aterixen®, ХС221GI