COVID-19 therapy: the efficacy and safety of combination of Ingavirin® with standard recommended treatment in real clinical practice

Aim of the study: estimation of the efficacy and safety of Ingavirin® inclusion in the recommended standard therapy for COVID-19 patients in real clinical practice. Material and methods. A prospective non-interventional study included hospitalized patients of both sexes aged 18-75 years with laboratory-confirmed diagnosis of moderate COVID-19, accompanied by specific bilateral changes in the lungs according to CT data with the need for oxygen therapy performance (category 4, WHO scale). The duration of the disease from the moment the first symptom appeared to the first dose of the study drug intake was «7 days, the period from the moment of hospitalization to the first dose intake was «48 h. Before the inclusion in the study, all patients were prescribed COVID-19 therapy - Ingavirin®, capsules, 90 mg and/or the standard therapy (ST) of COVID-19 recommended by the Ministry of Healthcare of Russia. Ingavirin® was prescribed in accordance with instructions for medical use: 2 capsules (180 mg) of the drug in the first 3 days and 1 capsule (90 mg) in the next 4 days, orally once a day, regardless of food intake. The condition of the patient was assessed at baseline (day -1/1 of the study), daily during the treatment period (days 2-7), on the 8th, as well as on 14±1 and 21±1 days of the study in person or by telephone interview, if the patient was discharged from the hospital. Results. 80 patients were included (40 persons in each of the two cohorts). The mean age of the study participants was 58, 15± 10,5 (56,73±10,19 in Ingavirin® + ST cohort, 59,58± 10,75 in the ST cohort). There were no significant differences in basic demographic and clinical data between cohorts (ANOVA, p <0,05). Time to the onset of clinical improvement, assessed by stable normalization of body temperature, respiratory rate and SpO2 (the main efficacy outcome), significantly decreased when Ingavirin® was added to standard therapy: 4,5±0,925 and 7,1±1,037 days, respectively (Mantel-Cox log-rank test: p=0,015; Breslow test: p=0,007; Tarone-Ware test: p=0,007). The proportion of patients with clinical improvement in the Ingavirin®+ST cohort was significantly higher than in the ST cohort by the 5th day of therapy (89,2% versus 64,1%, respectively; Fisher's exact test, p=0,015). The mean change (dynamics) in the severity category according to the WHO scale in the morning and in the evening in the Ingavirin® + ST cohort was significantly more evident than in the ST cohort (in the morning p=0,017; in the evening, p <0,001). The mean time to reaching 3rd category and below on the WHO scale was 10,34±1,025 days in the Ingavirin® + ST cohort and 14,96±0,974 days in the ST cohort (log-rank test: p=0,007; Breslow test: p=0,002; Tarone-Ware test: p=0,003). A decrease in the severity of the condition according to the WHO scale up to category 3 was fixed in 44,4% of patients in the Ingavirin® + ST cohort and in 10,5% in the ST cohort on the 6th day of therapy (Fisher's exact test, p=0,001). By the 7th day of treatment, an improvement in the patient's status according to the WHO scale was observed in 50% of cases in the Ingavirin® + ST cohort and in 18,4% in the ST cohort (Fisher's exact test, p=0,006). The mean time to reaching «2 points on the NEWS severity scale in the Ingavirin® +ST cohort was 5,233±0,847 days, in the ST cohort - 7,797±1,080 days (Mantel-Cox log-rank test: p=0,037; Tarone-Ware test: p=0,044 ). The proportion of patients with the need for oxygen support by 6 and 7 days of therapy in the Ingavirin® + ST cohort was 52,8% and 41,7%, respectively. In the ST cohort, the proportion of patients requiring oxygen therapy was significantly higher - 89,5% and 84,2%, respectively (Fisher's exact test, p=0,001 (6th day), p <0,001 (7th day)). The mean time to reaching SpO2 s95% was 6,401±1,096 days in the ST cohort and 3,625±0,823 in the Ingavirin® + ST cohort. The cohorts showed a significant statistical difference (log-rank test: p=0,020; Breslow test: p=0,022; Tarone-Ware test: p=0,012). The largest proportion of patients with a day and night cough score of «2 by the 3rd day of treatment was found in the Ingavirin® + ST cohort - 97,5% (compared to 80,5% in the ST cohort; Fisher's exact test, p=0,029). Conclusion: The inclusion of Ingavirin® in the scheme of recommended standard therapy for COVID-19 leads to a faster achievement of clinical improvement, an adequate level of saturation and positive integral clinical dynamics.

COVID-19, COVID-19, Ingavirin®, viral pneumonia, non-interventional study