N Yu Pshenichnaya1, V A Bulgakova2, N I Lvov3, A A Poromov4, E P Selkova5, A I Grekova6, I V Shestakova7, V V Maleev1, I A Leneva8. 1. Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare, Moscow, Russia. 2. Children's Health Research Centre, Ministry of Health of Russia, Moscow, Russia. 3. S.M. Kirov Military Medical Academy, Ministry of Defense of the Russian Federation, Saint Petersburg, Russia. 4. M.V. Lomonosov Moscow State University, Moscow, Russia. 5. G.N. Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare, Moscow, Russia. 6. Smolensk State Medical University, Ministry of Health of Russia, Smolensk, Russia. 7. A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia. 8. I.I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia.
Abstract
AIM: The aim of the study is to obtain additional data on safety and therapeutic efficacy of the antiviral drug Arbidol (umifenovir) in patients with a diagnosis of influenza and common cold. MATERIALS AND METHODS: Double-blind, randomized, placebo-controlled clinical study investigating efficacy and safety of Arbidol (umifenovir) in Treatment and Prophylaxis of Influenza and Common Cold (ARBITR) IV phase started in November 2011 and completed in April 2016 on the basis of 15 research centers in various regions of the Russian Federation. A total of 359 patients, aged 18 to 65 years with influenza or acute respiratory tract infection, of no more than 36 hours' duration were enrolled in the study. Patients were randomized into two groups: a group of patients (therapy group) treated by Arbidol (umifenovir) at a dosage of 800 mg/day (2 capsules) for 5 days (n=181), and a group of patients receiving placebo 4 times a day for 5 days (n=178). The primary outcome measures of the study were the duration of clinical illness among patients with common cold and influenza/ARVI, the duration and severity of the main symptoms. Number of clinical complications associated with influenza and common cold was assessed as a secondary outcome. Safety was assessed by analyzing number of adverse events that are probably or definitely related to Arbidol, assessing vital signs, examining the physical condition of patients and general clinical laboratory parameters. RESULTS: In the group treated by umifenovir, the number of full recover patients on the 4th day from the disease onset were significantly differed from the number of such cases in the placebo group. The number of cases of complete recovery after 96 hours was 98 patients (54.1%) and 77 (43.3%), p<0.05, and after 108 hours - 117 (64.6%) and 98 (55.1%), p<0.05. Duration of intoxication was reduced with umifenovir compared to placebo, amounted to 77.76 and 88.91 hours, respectively, p=0.013. The duration of all intoxication syndrome symptoms was also lower in the group receiving umifenovir. Thus, in the therapy group and placebo group, these parameters were respectively: fever duration - 67.96 and 75.32 hours (p=0.037), muscle pain - 52.23 and 59.08 hours (p=0.023), headache - 52.78 and 63.28 hours (p=0.013), weakness - 76.90 and 88.89 hours (p=0.008). The incidence of complications in the umifenovir group was 3.8%, in the placebo group 5.62%. Cases of acute tracheobronchitis was an increase in the placebo group (p<0.02). Umifenovir and placebo were well tolerated. A total of 42 cases of adverse events were registered in 11 patients in the treatment group and in 18 patients in the placebo group, which were not associated with umifenovir or placebo. CONCLUSION: The results of this study indicate umifenovir safety and confirm its effectiveness to the treatment of influenza and other acute respiratory viral infections in adult patients. It was found that effect of umifenovir in the treatment of influenza in adults is most pronounced in the acute stage of the disease and appears in the reduction of time to resolution of all symptoms of the disease, reducing the severity of symptoms of the disease.
RCT Entities:
AIM: The aim of the study is to obtain additional data on safety and therapeutic efficacy of the antiviral drug Arbidol (umifenovir) in patients with a diagnosis of influenza and common cold. MATERIALS AND METHODS: Double-blind, randomized, placebo-controlled clinical study investigating efficacy and safety of Arbidol (umifenovir) in Treatment and Prophylaxis of Influenza and Common Cold (ARBITR) IV phase started in November 2011 and completed in April 2016 on the basis of 15 research centers in various regions of the Russian Federation. A total of 359 patients, aged 18 to 65 years with influenza or acute respiratory tract infection, of no more than 36 hours' duration were enrolled in the study. Patients were randomized into two groups: a group of patients (therapy group) treated by Arbidol (umifenovir) at a dosage of 800 mg/day (2 capsules) for 5 days (n=181), and a group of patients receiving placebo 4 times a day for 5 days (n=178). The primary outcome measures of the study were the duration of clinical illness among patients with common cold and influenza/ARVI, the duration and severity of the main symptoms. Number of clinical complications associated with influenza and common cold was assessed as a secondary outcome. Safety was assessed by analyzing number of adverse events that are probably or definitely related to Arbidol, assessing vital signs, examining the physical condition of patients and general clinical laboratory parameters. RESULTS: In the group treated by umifenovir, the number of full recover patients on the 4th day from the disease onset were significantly differed from the number of such cases in the placebo group. The number of cases of complete recovery after 96 hours was 98 patients (54.1%) and 77 (43.3%), p<0.05, and after 108 hours - 117 (64.6%) and 98 (55.1%), p<0.05. Duration of intoxication was reduced with umifenovir compared to placebo, amounted to 77.76 and 88.91 hours, respectively, p=0.013. The duration of all intoxication syndrome symptoms was also lower in the group receiving umifenovir. Thus, in the therapy group and placebo group, these parameters were respectively: fever duration - 67.96 and 75.32 hours (p=0.037), muscle pain - 52.23 and 59.08 hours (p=0.023), headache - 52.78 and 63.28 hours (p=0.013), weakness - 76.90 and 88.89 hours (p=0.008). The incidence of complications in the umifenovir group was 3.8%, in the placebo group 5.62%. Cases of acute tracheobronchitis was an increase in the placebo group (p<0.02). Umifenovir and placebo were well tolerated. A total of 42 cases of adverse events were registered in 11 patients in the treatment group and in 18 patients in the placebo group, which were not associated with umifenovir or placebo. CONCLUSION: The results of this study indicate umifenovir safety and confirm its effectiveness to the treatment of influenza and other acute respiratory viral infections in adult patients. It was found that effect of umifenovir in the treatment of influenza in adults is most pronounced in the acute stage of the disease and appears in the reduction of time to resolution of all symptoms of the disease, reducing the severity of symptoms of the disease.
Authors: Elena V Proskurnina; Dmitry Yu Izmailov; Madina M Sozarukova; Tatiana A Zhuravleva; Irina A Leneva; Artem A Poromov Journal: Molecules Date: 2020-03-30 Impact factor: 4.411