This multicenter, double-blind, placebo-controlled clinical trial was conducted to obtain additional data on the efficacy and safety of Anaferon for the treatment of acute respiratory viral infections (ARVI) during seasonal increase in their incidence (RCT of the Ministry of Health of Russia No 356 dated 24.07.2018; ClinicalTrials.gov Identifier: NCT03707912). Patients and methods. Between October 2018 and March 2019, a total of 204 patients aged 18 to 70 years with ARVI symptoms were included in this study within the first 24 hours of symptom onset. Patients were randomized into 2 groups: 104 individuals received oral Anaferon (should be kept in the mouth until completely dissolved and without food) according to the following scheme: 1 tablet every 30 minutes during the first 2 hours; then 3 more doses at regular intervals during the first day; then 1 tablet 3 times a day on days 2–5; 100 individuals received placebo according to the same scheme. The primary endpoint was time to resolution of symptoms of clinically diagnosed and/or PCR (polymerase chain reaction) – confirmed ARVI. Addithional endpoints included: time to resolution of symptoms of ARVI confirmed by PCR; proportion of patients with resolution of symptoms of clinically diagnosed and/or PCR-confirmed ARVI and separately PCR-confirmed ARVI; severity of clinically diagnosed and/or PCR-confirmed ARVI (assessed by ‘area under the curve’ for the total severity index); the number of antipyretic doses taken according to indications on days 1–3 of treatment (checked in the patient's diary); proportion of patients who required antibiotic treatment on days 4–7 of follow-up. To assess safety, we analyzed the incidence and type of adverse events (AEs), their severity, association with drug use, and treatment outcome. The following statistical methods were used: Fisher's exact test, Cochran–Mantel–Haenszel test, Wilcoxon test, and repeated measures ANOVA, PROC MIXED. Results. A total of 203 patients were included in the intention-to-treat (ITT) and per protocol (РР) analysis: 103 [95] individuals in the Anaferon arm and 100 [93] individuals in the Placebo arm. Patients receiving Anaferon had significantly shorter time to resolution of all ARVI symptoms than patients receiving placebo: 4.1 ± 1.6 days vs 4.5 ± 1.5 days (p = 0.032). The disease was on average 1 day shorter in patients from the experimental group compared to controls: 3.6 ± 1.5 days vs 4.6 ± 1.5 days (p = 0.007). The proportion of patients who had resolution of symptoms of clinically diagnosed and/or PCR-confirmed ARVI was significantly higher in the Anaferon arm compared to Placebo arm (p = 0.0012). Among patients with PCR-verified ARVI, treatment with Anaferon resulted in twice as frequent recovery as in the control group on day 4 (53.7% vs 26.3%) and day 7 (70.7% vs 36.8%). In the Anaferon arm, we observed shorter disease duration and higher proportion of patients recovered compared to the Placebo arm; however, patients in both groups had a similar need for antipyretic drugs on days 1–3 of treatment, as well as for antibiotic therapy. The incidence of AEs in the Anaferon and Placebo groups did not vary significantly. No AEs with a reliable association with Anaferon were registered. Conclusion. Our findings suggest high efficacy and safety of Anaferon in patients with ARVI. The best results were obtained in patients with PCR-verified diagnosis, which can be attributed to the involvement of the interferon system in the action of the drug. The results of this RCT confirm the data obtained in previous studies and long-term clinical experience of using Anaferon. Key words: acute respiratory viral infections, ARVI, treatment, effective therapy, placebo-controlled study, Anaferon, randomized clinical trial, comprehensive therapy, efficacy, safety
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