[Non-specific prevention of COVID-19 during vaccination against a new coronavirus infection: results of a multicenter, double-blind, placebo-controlled, randomized clinical trial].

ABSTRACT

BACKGROUND: A multicenter, double-blind, placebo-controlled, randomized clinical trial (RCT) of the phase III efficacy and safety of Ergoferon® for the non-specific prevention of COVID-19 during vaccination against a new coronavirus infection was conducted (permission of the Ministry of Health of the Russian Federation №559 dated 22.09.2021; ClinicalTrials.gov Identifier NCT05069649). AIM: To evaluate the efficacy and safety of the use of Ergoferon for the non-specific prevention of COVID-19 during vaccination against a new coronavirus infection. MATERIALS AND METHODS: From October 2021 to April 2022, 1,057 patients aged 18 to 92 years who received component I of the "Gam-COVID-Vac" vaccine were included. After screening, 1,050 patients were randomized into 2 groups 526 people received Ergoferon according to the prophylactic scheme - 1 tablet per administration 2 times a day for 3 weeks, the drug is not allowed during the meal and should be kept in the mouth without swallowing, until completely dissolved; 524 patients received a placebo according to the Ergoferon® scheme. The total duration of participation in the study was 5 weeks + 3 days. The primary endpoint is the number of RT-PCR - confirmed cases of SARS-CoV-2 infection, regardless of the presence of symptoms during participation in the study. An additional criterion of effectiveness is the proportion of those hospitalized with COVID-19. The safety assessment included consideration of the presence and nature of adverse events (AEs), their severity, relationship with the drug intake, and outcome. Statistical data processing was carried out using SAS 9.4 with the calculation of the exact Fisher test, χ2 test, Cochrane-Mantel-Hensel test, Wilcoxon test and other parameters. RESULTS: The ITT (Intention-to-treat) and PP [Per Protocol] efficacy analysis included data from 1,050 [970] patients 526 [489] people - Ergoferon® group and 524 [481] people - Placebo group. The primary endpoint - the number of laboratory-confirmed cases of SARS-CoV-2 infections was 3 times less compared to placebo - 7 (1.43%) vs 22 (4.57%), respectively (p=0.0046; [p=0.0041]). Taking Ergoferon® reduces the risk of SARS-CoV-2 infection by more than 3 times in vaccinated patients during 5 weeks of the vaccination and post-vaccination periods (p=0.0046 [p=0.0041]). Of the COVID-19 patients in the Ergoferon® group (1.33%) nobody was hospitalized. According to the Post hoc analysis, Ergoferon® reduces the risk of COVID-19 disease by 4 times in the period between the components I and II of the "Gam-COVID-Vac" vaccine (p=0.0066 [p=0.006]). The frequency of AEs in both groups did not differ. There were no registered AEs associated with the drug with a reliable degree. There was a high level of patient compliance and good tolerability. CONCLUSION: Ergoferon is an effective and safe drug for the prevention of COVID-19 in people vaccinated against a new coronavirus infection.