Safety Of Favipiravir Research Articles

Efficacy and safety of favipiravir and remdesivir in COVID-19 patients: Clinical data

Aim. To evaluate the efficacy and safety of favipiravir and remdesivir in the infectious disease hospital of the Volgograd region in 2022. Materials and methods. In total, 559 medical records of patients prescribed favipiravir or remdesivir in 2022 were studied. Long-term results of the drug use and disease outcomes after discharge or transfer to another medical institution were assessed using the Federal registry of people with COVID-19. Results. Favipiravir was more frequently prescribed in mild cases of the disease. After excluding patients without signs of lung injury from the analysis, there were no significant differences in mortality and improvement. Patients receiving favipiravir had lower odds of ALT elevations above 5 upper limits of normal and developing drug-induced liver injury with a possible RUCAM score compared with patients receiving remdesivir (OR = 0.40, 95CI 0.20–0.80 and OR = 0.30, 95 CI 0.08–1.08). Conclusion. The limited experience of the use of favipiravir for COVID-19 necessitates further research into its efficacy and safety, particularly when prescribing warfarin and high doses of direct anticoagulants simultaneously.

Assessment of the efficacy and safety of favipiravir in patients with SARS-CoV-2 infection in United Arab Emirates: A single-center study

Assessment of the efficacy and safety of favipiravir in patients with SARS-CoV-2 infection in United Arab Emirates: A single-center study

Clinical and economic evaluation of the use of favipiravir in treatment regimens for COVID-19

Background. Currently, sufficient information has been accumulated the literature on the clinical effectiveness and safety of favipiravir in adult patients with COVID-19, including cases of its use in intensive care units and in comorbid patients. This article sum­marizes the latest published data from clinical studies, systematic reviews and meta-analyses, including data from real-life clinical prac­tice. A number of studies have conducted a pharmacoeconomic evaluation of the use of favipiravir in adult patients with COVID-19. Objective. To evaluate pharmacoeconomic efficacy of the use of favipiravir in adult patients with non-severe forms of COVID-19 in a Rus­sian hospital seetings. Materials and methods. On the basis of the clinic of the Russian University of Medicine a non-interventional clinical study was per­formed, including 201 patients with mild COVID-19. Patients were divided into two groups: with favipiravir therapy or without it. Results. A reduction in hospitalization time by 2 days was demonstrated in patients with COVID-19 receiving favipiravir, which leads to the reduction in hospitalization costs for 1 patient in the amount of RUB 16,643.69. Conclusions. Thus, various data on the use of favipiravir for COVID-19 allow us to demonstrate pharmacoeconomic benefits, both in terms of budgetary savings and a positive impact on reducing the burden on the healthcare system and improving key medical statistics, including morbidity and mortality.

Safety and efficacy of favipiravir in COVID-19 patients with pneumonia. A randomized, double-blind, placebo-controlled study (FAVID).

To design a randomized clinical trial to assess the efficacy and safety of favipiravir in patients with COVID-19 disease with pneumonia. A randomized, double blind, placebo-controlled clinical trial of favipiravir in patients with COVID-19 pneumonia was conducted in three Spanish sites. Randomization 1:1 to favipiravir or placebo (in both groups added to the Standard of Care) was performed to treat the patients with COVID-19 pneumonia. The primary endpoint was "time to clinical improvement," measured as an improvement for ≥ two categories on a 7-point WHO ordinal scale in an up to 28 days' time frame. Forty-four patients were randomized (23 in the favipiravir group and 21 in the placebo group). The median time to clinical improvement was not different between the favipiravir and the placebo arms (10 days for both groups) and none of the secondary endpoints showed significant differences between arms. The proportion of adverse events (both serious and non-serious) was statistically different between the favipiravir group (68.29%) and the placebo group (31.7%) (p = 0.019), but there was insufficient statistical evidence to correlate the degree of severity of the events with the treatment group. Favipiravir administered for ten days to patients with COVID-19 and pneumonia did not improve outcomes compared with placebo. Although this is an underpowered negative study, efficacy results align with other randomized trials. However, in the present study, the non-serious adverse events were more frequent in the favipiravir group.

When antivirals backfire: An evaluation of favipiravir’s clinical outcomes in critically ill patients with COVID-19: A multicenter cohort study

BackgroundFavipiravir is an oral antiviral, that might treat COVID-19 by enhancing viral eradication, particularly in patients with mild-to-moderate disease. Yet, the findings on the use of favipiravir in critically ill patients with COVID-19 are inconsistent. Therefore, this study aimed to assess the effectiveness and safety of favipiravir in critically ill patients with COVID-19. MethodA multicenter retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the intensive care units (ICUs) was conducted from March 2020 to July 2021. Patients were categorized based on favipiravir use (control vs. favipiravir). The primary outcome was in-hospital mortality. Secondary outcomes included mechanical ventilation (MV) duration, 30-day mortality, ICU length of stay (LOS), hospital LOS, and complications during the stay. ResultsAfter propensity score (PS) matching (1:1 ratio), 146 patients were included in the final analysis. A higher in-hospital and 30-day mortality were observed in patients receiving favipiravir compared to the control group at crude analysis (65.3% vs. 43.8%; P-value=0.009 and 56.3% vs. 40.3; P-value=0.06, respectively); however, no differences were observed using multivariable Cox proportional hazards regression analysis (HR 1.17; 95% CI 0.73, 1.87; P-value =0.51 and HR 0.86; 95% CI 0.53, 1.39; P-value=0.53, respectively). Conversely, the MV duration and ICU LOS were longer in patients who received favipiravir than the control group (β coefficient 0.51; CI 0.09, 0.92; P-value = 0.02, β coefficient 0.41; CI 0.17, 0.64; P-value = 0.0006, respectively). Complications during the stay were comparable between the two groups. ConclusionThe use of favipiravir in critically ill patients with COVID-19 did not demonstrate a reduction in mortality; instead, it was linked with longer MV duration and ICU stay. This finding suggests limiting favipiravir use to infections where it is more effective, other than COVID-19. Further randomized clinical trials are needed to confirm these findings.

Multicenter, single-blind, randomized controlled study of the efficacy and safety of favipiravir and nafamostat mesilate in patients with COVID-19 pneumonia

ObjectivesTo evaluate the efficacy and safety of nafamostat combined with favipiravir for the treatment of COVID-19. MethodsWe conducted a multicenter, randomized, single-blind, placebo-controlled, parallel assignment study in hospitalized patients with mild-to-moderate COVID-19 pneumonia. Patients were randomly assigned to receive favipiravir alone (n = 24) or nafamostat with favipiravir (n = 21). The outcomes included changes in the World Health Organization clinical progression scale score, time to improvement in body temperature, and improvement in oxygen saturation (SpO2). ResultsThere was no significant difference in the changes in the clinical progression scale between nafamostat with favipiravir and favipiravir alone groups (median, -0.444 vs -0.150, respectively; least-squares mean difference, -0.294; P = 0.364). The time to improvement in body temperature was significantly shorter in the combination group (5.0 days; 95% confidence interval, 4.0-7.0) than in the favipiravir group (9.0 days; 95% confidence interval, 7.0-18.0; P =0.009). The changes in SpO2 were greater in the combination group than in the favipiravir group (0.526% vs -1.304%, respectively; least-squares mean difference, 1.831; P = 0.022). No serious adverse events or deaths were reported, but phlebitis occurred in 57.1% of the patients in the combination group. ConclusionAlthough our study showed no differences in clinical progression, earlier defervescence, and recovery of SpO2 were observed in the combination group.

Real-World Experience with Favipiravir for the Treatment of Mild-to-Moderate COVID-19 in India.

BackgroundFavipiravir, an RNA-dependent RNA polymerase inhibitor (RdRp), is a broad-spectrum oral antiviral agent approved in India under emergency use authorization, for the treatment of mild-to-moderate coronavirus disease (COVID-19). The present study was planned to evaluate the effectiveness and safety of favipiravir in real-world clinical practice.Materials and MethodsThis was a multicentric, retrospective, single-arm study conducted across four centres in India, after obtaining permission from the independent ethics committee. Medical records were analysed to evaluate effectiveness and safety of patients who were prescribed favipiravir.ResultsThe medical records of a total of 360 patients met the inclusion criteria, with 358 of them available for the final analysis. Males made up 58.46% of the study population. The average age of enrolled patients was 51.80 ± 16.45 years. The most common symptoms were fever, cough, and myalgia-fatigue. The median time to clinical cure and fever relief was five and four days, respectively. The average length of stay in the hospital was six days. In total, 8% of the patients experienced adverse events. Hepatic enzyme elevation, diarrhoea, decreased appetite, headache, fatigue, and giddiness were the common symptoms.ConclusionIn our real-world study, favipiravir was found to have a clinical cure rate of more than 90% in mild-to-moderate COVID-19 patients. This supports the use of favipiravir in the treatment of COVID-19. Favipiravir was well tolerated, with only minimal side effects, which were transient in nature.

Efficacy and safety of favipiravir plus interferon‐beta versus lopinavir/ritonavir plus interferon‐beta in moderately ill patients with COVID‐19: A randomized clinical trial

Favipiravir (FVP), lopinavir/ritonavir (LPV/RTV), and interferon‐beta (INF‐beta) are considered as potential treatments for COVID‐19. We examined the efficacy and safety of FVP and INF‐beta compared to LPV/RTV and INF‐beta combinations for the treatment of SARS‐CoV‐2. It was a single‐center randomized clinical trial. Eligible patients were randomized to receive FVP plus INF‐beta versus LPV/RTV plus INF‐beta. The primary endpoint was the viral clearance after seven days of randomization. ICU admission, length of stay (LOS) in hospital, in‐hospital mortality, and the incidence of adverse events were also measured. This trial was registered on the Iranian Registry of Clinical Trials (IRCT20200506047323N3). Patients were randomly allocated to the FVP (n = 33) and LPV/RTV (n = 33) groups. The viral clearance on Day seven was not significantly different between the FVP (31.1%) and the LPV/RTV groups (16.1%). The rate of ICU admission and likewise the in‐hospital mortality in the FVP group (12.5% and 6.3%, respectively) were similar to the LPV/RTV groups (19.4% and 19.4%, respectively). The median LOS in the hospital was also not different (6.8 days [interquartile range; IQR = 5.0–11.0] in the FVP and (8.0 days [IQR = 5.5–12.5]) in LPV/RTV groups (p = 0.140). Adverse events were observed in 25.0% of FVP and 32.3% of LPV/RTV groups. The combination therapy with FVP did not exert a higher efficacy compared to the combination regimen of LPV/RTV. However, both treatment regimens demonstrated a mild profile of adverse events.

EFFECTIVENESS AND SAFETY OF FAVIPIRAVIR INFUSION IN PATIENTS HOSPITALIZED WITH COVID-19

Research in the development of new therapeutic agents with a wide spectrum of the antiviral activity and a low ability to develop resistance remains the main dimension in combating the global threat to public health. The need for a parenteral form of favipiravir was dictated by the necessity to increase the efficacy of therapy in COVID-19 inpatients. This dosage form has expanded the possibilities of drug therapy in the inpatients, for whom a therapeutic effect acceleration and a high safety profile of the drugs used are especially important.The aim of the article is the evaluation of the efficacy and safety of a medicinal product containing favipiravir for the parenteral administration against the background of pathogenetic and symptomatic therapy, in comparison with standard therapy in hospitalized COVID-19 patients.Materials and methods. An open, randomized, multicenter comparative study was conducted in 6 research centers in the Russian Federation to evaluate the efficacy and safety of favipiravir, a lyophilisate for the preparation of a concentrate for the infusion solution administrated to the patients hospitalized with COVID-19. Screening procedures and randomization were completed in 217 patients, 209 of which had completed the study in accordance with the protocol.Results. Between the study groups, statistically significant differences have been found out, making it possible to consider the hypothesis of the drug Areplivir (favipiravir) superiority for the parenteral administration over the standard therapy, which included favipiravir (p. o.) and remdesivir. A comparative analysis has shown that a course of therapy with the parenteral favipiravir drug leads to a significant improvement in the condition of patients with COVID-19, significant benefits in terms of the speed and frequency of improvement in the clinical status of patients, as well as a reduction in the hospital stay length. It has been proven that therapy with a drug containing favipiravir for the parenteral administration does not adversely affect the parameters of clinical and biochemical blood tests, urinalysis, coagulograms, vital signs and ECG, which indicates the therapy safety. The study drug is characterized by a high safety profile and tolerability.Conclusion. The versatility and resistance to mutations of RNA-dependent RNA polymerase make it possible to consider it as the main target for combating the most common RNA viruses that cause ARVI, that determines the need further studies of favipiravir to expand the range of its indications.

Overview of clinical outcome and therapeutic effectiveness of Favipiravir in patients with COVID-19 admitted to intensive care unit, Riyadh, Saudi Arabia

BackgroundPrior to the availability of the current COVID-19 vaccine, the need to control the pandemic worldwide was focused on management of the disease using previously approved antivirals, including Favipiravir which inhibits viral replication through the RNA dependent RNA polymerase enzyme. Favipiravir’s efficacy against different viral infections has made it a potential treatment for COVID-19. We are aiming in this study to assess the therapeutic efficacy and safety of Favipiravir in treating critically ill patients admitted with COVID-19 to Intensive Care Units (ICUs). MethodsThis is a retrospective cohort study was conducted in five tertiary hospitals in Riyadh, Kingdom of Saudi Arabia (KSA). The studied sample was randomized from a huge pool of data collected primarily for critically ill COVID-19 patients admitted to (ICUs) during the period between April 2020 to March 2021. Two groups of patients matched 1: 1 for age and body mass index (BMI) was enrolled in the study; one group received Favipiravir and another comparison group received other antimicrobial medications, not including Favipiravir. ResultsA total data of 538 COVID-19 patients were analyzed, 269 (50.%) received Favipiravir and 269 (50%) the control group received different treatments. More than two-thirds 201 (74.7%) were Saudi citizens, the majority 177 (65.8%) were males and the mean age and (BMI) were; (57.23 ± 15.16) years and (31.61 ± 7.33) kg/m2 respectively. The most frequent symptoms of presentation were shortness of breath (SOB), fever, and cough, and the most frequent comorbidity was diabetes mellitus, hypertension, and ischemic heart disease.In the supplemental therapy, corticosteroid, tocilizumab and chloroquine were statistically significant (P = 0.001) when combined in the FVP group more than in the comparison group. Severe acute respiratory distress syndrome (ARDS) was more frequent among Favipiravir group, while the overall mortality rate among the Favipiravir group was not statistically significant (p-value 0.4). ConclusionAccording to the study’s results revealing FVP is not superior to other antivirals, patients who received Favipiravir presented with more severe symptoms, more comorbidities, more complications, and is not effective in controlling the cytokine storm which negatively impact the efficacy of Favipiravir.FVP therapy had no influence on ICU and hospital length of stay in comparison with the control group as well as in the overall mortality rate among the FVP group was not statistically significant. further research is needed to understand how FVP along with other treatments can improve the length of stay among COVID-19 patients admitted to the ICU.

Addendum: The efficacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials

Addendum: The efficacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials

The Effectiveness and Safety of Favipiravir in COVID-19 Hospitalized Patients at Tertiary Referral Hospital, Bali, Indonesia

COVID-19 is a major public health problem, with still questionable specific cure. Favipiravir is a COVID-19 antiviral that is potentially a therapy for COVID-19. This study aimed to analyze its effectivity and safety in moderate to critical hospitalized patients. This study was a retrospective cohort in a tertiary referral hospital in Denpasar City, Bali Province, Indonesia, from August 2020 to January 2021. There was a total of 192 patients; 96 in the favipiravir group and 96in the non-favipiravir group (remdesivir/oseltamivir). Effectivity was measured by assessing the clinical condition at the end of the isolation period of 14 days. The favipiravir group showed better clinical conditions than the non-favipiravir group (79.2% vs. 56.3%; adjusted RR = 2.196; 95% CI = 1.084 – 4.451; p-value= 0.029), seen from being free of fever and respiratory problems. Stratification analysis demonstrated that the clinical improvement was significantly differentin the severe/critical group in favor of favipiravir (RR = 1.573; 95% CI = 1.139-2.172). The most common non-serious adverse events (AE) found in the use offavipiravir were gastrointestinal disturbances (12.5%). In brief, favipiravir is effective in severe/critical cases, and less serious AE were found in its use. Appropriate treatment is expected to help in reducing the public health burden.

P5‐64: Therapeutic effectiveness & safety of favipiravir in COVID‐19 patients with risk factors for mortality: Clinical practice experience from India

P5‐64: Therapeutic effectiveness & safety of favipiravir in COVID‐19 patients with risk factors for mortality: Clinical practice experience from India

Favipiravir Versus Arbidol for Clinical Recovery Rate in Moderate and Severe Adult COVID-19 Patients: A Prospective, Multicenter, Open-Label, Randomized Controlled Clinical Trial.

Background: In addition to supportive therapy, antiviral therapy is an effective treatment for coronavirus disease 2019 (COVID-19).Objective: To compare the efficacy and safety of favipiravir and umifenovir (Arbidol) to treat COVID-19 patients.Methods: We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Enrolled patients with initial symptoms within 12 days were randomly assigned in a 1:1 ratio to receive conventional therapy plus Arbidol (200 mg*3/day) or favipiravir (1600 mg*2/first day followed by 600 mg*2/day) for 7 days. The primary outcome was the clinical recovery rate at day 7 of drug administration (relief for pyrexia and cough, respiratory frequency ≤24 times/min; oxygen saturation ≥98%). Latency to relief for pyrexia and cough and the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV)/mechanical ventilation (MV) were the secondary outcomes. Safety data were collected for 17 days.Results: A total of 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive favipiravir (116 assessed), and 120 patients were assigned to receive Arbidol (120 assessed). The clinical recovery rate at day 7 of drug administration did not significantly differ between the favipiravir group (71/116) and Arbidol group (62/120) (p = 0.1396, difference in recovery rate: 0.0954; 95% CI: −0.0305∼0.2213). Favipiravir contributed to relief for both pyrexia (difference: 1.70 days, p < 0.0001) and cough (difference: 1.75 days, p < 0.0001). No difference was observed in the AOT or NMV/MV rate (both p > 0.05). The most frequently observed favipiravir-associated adverse event was increased serum uric acid (16/116, OR: 5.52, p = 0.0014).Conclusion: Among patients with COVID-19, favipiravir, compared to Arbidol, did not significantly improve the clinical recovery rate at day 7. Favipiravir significantly improved the latency to relieve pyrexia and cough. Adverse effects caused by favipiravir are mild and manageable.

Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial.

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-controlled trial. We conducted a randomized, single-blind, placebo-controlled Phase III trial assessing the efficacy and safety of favipiravir in patients with moderate pneumonia not requiring oxygen therapy.MethodsCOVID-19 patients with moderate pneumonia (SpO2 ≥ 94%) within 10 days of onset of fever (temperature ≥ 37.5 °C) were assigned to receive either placebo or favipiravir (1800 mg twice a day on Day 1, followed by 800 mg twice a day for up to 13 days) in a ratio of 1:2. An adaptive design was used to re-estimate the sample size. The primary endpoint was a composite outcome defined as the time to improvement in temperature, oxygen saturation levels (SpO2), and findings on chest imaging, and recovery to SARS-CoV-2-negative. This endpoint was re-examined by the Central Committee under blinded conditions.ResultsA total of 156 patients were randomized. The median time of the primary endpoint was 11.9 days in the favipiravir group and 14.7 days in the placebo group, with a significant difference (p = 0.0136). Favipiravir-treated patients with known risk factors such as obesity or coexisting conditions provided better effects. Furthermore, patients with early-onset in the favipiravir group showed higher odds ratio. No deaths were documented. Although adverse events in the favipiravir group were predominantly transient, the incidence was significantly higher.ConclusionsThe results suggested favipiravir may be one of options for moderate COVID-19 pneumonia treatment. However, the risk of adverse events, including hyperuricemia, should be carefully considered.Trial registrationClinicaltrials.jp number: JapicCTI-205238.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00517-4.

The efficacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials

The novel coronavirus outbreak began in late December 2019 and rapidly spread worldwide, critically impacting public health systems. A number of already approved and marketed drugs are being tested for repurposing, including Favipiravir. We aim to investigate the efficacy and safety of Favipiravir in treatment of COVID-19 patients through a systematic review and meta-analysis. This systematic review and meta-analysis were reported in accordance with the PRISMA statement. We registered the protocol in the PROSPERO (CRD42020180032). All clinical trials which addressed the safety and efficacy of Favipiravir in comparison to other control groups for treatment of patients with confirmed infection with SARS-CoV2 were included. We searched electronic databases including LitCovid/PubMed, Scopus, Web of Sciences, Cochrane, and Scientific Information Database up to 31 December 2020. We assessed the risk of bias of the included studies using Cochrane Collaboration criteria. All analyses were performed using the Comprehensive Meta-Analysis software version 2, and the risk ratio index was calculated. Egger and Begg test was used for assessing publication bias. Nine studies were included in our meta-analysis. The results of the meta-analysis revealed a significant clinical improvement in the Favipiravir group versus the control group during seven days after hospitalization (RR = 1.24, 95% CI: 1.09–1.41; P = 0.001). Viral clearance was more in 14 days after hospitalization in Favipiravir group than control group, but this finding marginally not significant (RR = 1.11, 95% CI: 0.98–1.25; P = 0.094). Requiring supplemental oxygen therapy in the Favipiravir group was 7% less than the control group, (RR = 0.93, 95% CI: 0.67–1.28; P = 0.664). Transferred to ICU and adverse events were not statistically different between two groups. The mortality rate in the Favipiravir group was approximately 30% less than the control group, but this finding not statistically significant. Favipiravir possibly exerted no significant beneficial effect in the term of mortality in the general group of patients with mild to moderate COVID-19. We should consider that perhaps the use of antiviral once the patient has symptoms is too late and this would explain their low efficacy in the clinical setting.

Favipiravir Effects on the Control of Clinical Symptoms of Hospitalized COVID-19 Cases: An Experience with Iranian Formulated Dosage Form.

Coronavirus disease -19 (COVID-19) pandemic, caused by SARS-CoV-2, has gradually spread worldwide, becoming a major public health event. This situation requires designing a novel antiviral agent against the SARS-CoV-2; however, this is time-consuming and the use of repurposed medicines may be promising. One such medicine is favipiravir, primarily introduced as an anti-influenza agent in east world. The aim of this study was to evaluate the efficacy and safety of favipiravir in comparison with lopinavir-ritonavir in SARS-CoV-2 infection. In this randomized clinical trial, 62 patients were recruited. These patients had bilateral pulmonary infiltration with peripheral oxygen saturation lower than 93%. The median time from symptoms onset to intervention initiation was seven days. Favipiravir was not available in the Iranian pharmaceutical market, and it was decided to formulate it at the research laboratory of School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients received favipiravir tablet at a dose of 1600 mg orally twice a day for day one and then 600 mg orally twice a day for days 2 to 6. In the second group, the patients received lopinavir-ritonavir combination tablet at a dose of 200/50 mg twice a day for seven days. Fever, cough, and dyspnea were improved significantly in favipiravir group in comparison with lopinavir-ritonavir group on days four and five. Mortality rate and ICU stay in both groups were similar, and there was no significant difference in this regard (P = 0.463 and P = 0.286, respectively). Chest X-ray improvement also was not significantly different between the two groups. Adverse drug reactions occurred in both groups, and impaired liver enzymes were the most frequent adverse effect. In conclusion, early administration of oral favipiravir may reduce the duration of clinical signs and symptoms in patients with COVID-19 and hospitalization period. The mortality rate also should be investigated in future clinical trials.

Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial

ObjectiveTo assess the efficacy and safety of favipiravir in adults with mild-to-moderate coronavirus disease 2019 (COVID-19). MethodsIn this randomized, open-label, parallel-arm, multicenter, phase 3 trial, adults (18–75 years) with RT-PCR confirmed COVID-19 and mild-to-moderate symptoms (including asymptomatic) were randomized 1:1 to oral favipiravir (day 1: 1800 mg BID and days 2−14: 800 mg BID) plus standard supportive care versus supportive care alone. The primary endpoint was time to the cessation of viral shedding; time to clinical cure was also measured. ResultsFrom May 14 to July 3, 2020, 150 patients were randomized to favipiravir (n = 75) or control (n = 75). Median time to the cessation of viral shedding was 5 days (95% CI: 4 days, 7 days) versus 7 days (95% CI: 5 days, 8 days), P = 0.129, and median time to clinical cure was 3 days (95% CI: 3 days, 4 days) versus 5 days (95% CI: 4 days, 6 days), P = 0.030, for favipiravir and control, respectively. Adverse events were observed in 36% of favipiravir and 8% of control patients. One control patient died due to worsening disease. ConclusionThe lack of statistical significance on the primary endpoint was confounded by limitations of the RT-PCR assay. Significant improvement in time to clinical cure suggests favipiravir may be beneficial in mild-to-moderate COVID-19.

Favipiravir and COVID-19: A Simplified Summary.

A recent outbreak of coronavirus disease 2019 (COVID-19) caused by the novel coronavirus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in Wuhan, China, at the end of 2019 and then spread rapidly all over the world. However, there are no specific antiviral therapies for COVID-19, using the agents which approved or in development for other viral infections is one of the potentially quickest ways to find treatment for this new viral infection. Favipiravir is an effective agent that acts as a nucleotide analog that selectively inhibits the viral RNA dependent RNA polymerase or causes lethal mutagenesis upon incorporation into the virus RNA. In view of recent studies and discussion on favipiravir, in this mini review we aimed to summarize the clinical trials studying the efficacy and safety of favipiravir in patients with COVID-19.

Особенности коронавирусной инфекции COVID-19 и возможности раннего начала этиотропной терапии. Результаты клинического применения фавипиравира

This paper provides the results of a study evaluating the efficacy and safety of etiotropic therapy in patients hospitalized with SARS-CoV-2 infection. Objective. Тo evaluate the efficacy and safety of favipiravir (Areplivir) in patients with coronavirus disease 2019 (COVID-19) and compare it with recommended standard therapy. Patients and methods. Two hundred men and women aged between 18 and 80 years with COVID-19 were randomized into this study. The experimental group included patients who received favipiravir, whereas the control group comprised patients who received causal therapy in accordance with the latest version of the temporary methodical recommendations of the Ministry of Health of Russia ‘Prevention, diagnosis, and treatment of coronavirus infection (COVID-19).’ The efficacy and safety of therapy were evaluated by assessing clinical improvement using the WHO Ordinal Scale for Clinical Improvement, clinical and laboratory parameters, findings of chest computed tomography (CT), and elimination of SARS-CoV-2. We also analyzed the frequency and type of adverse events, need for invasive and non-invasive ventilation, and death rates. Results. Our analysis has demonstrated significant benefits of favipiravir over standard therapy in terms of the time to clinical improvement (in the experimental group it was 4 days shorter on average), time to recovery, frequency of recovery after 10 days (44% of patients from the experimental group and 10% of patients from the control group had no clinical signs of the disease at this time-point), and frequency of virus elimination by day 10 of therapy. Treatment with favipiravir was associated with a significant improvement in the lung condition (according to CT), normalization of laboratory parameters, and saturation level. Favipiravir has demonstrated a good safety profile similar to that of standard therapy. There was no difference in the frequency of adverse events between the experimental and control groups. Conclusion. The use of favipiravir for the treatment of SARS-CoV-2 infection reduced the time to clinical improvement by 4 days on average compared to standard therapy, ensured improvement of the lung condition (according to CT scans), and facilitated virus elimination in more than 90% of patients, thereby promoting faster recovery. Favipiravir had a good safety profile and was well tolerated by patients. This treatment regimen was shown to be effective, sufficient, and clinically reasonable to achieve good outcomes. Timely initiation of therapy with favipiravir (Areplivir) improves disease prognosis and reduces the global socioeconomic burden of the current pandemic. Key words: COVID-19, Areplivir, coronavirus, causal therapy, favipiravir