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

Abstract

The novel coronavirus outbreak began in late December 2019 and rapidly spread worldwide, critically impacting public health systems. Several already approved and marketed drugs are being tested for repurposing, including Favipiravir. We aim to investigate the efficacy and safety of Favipiravir in the treatment of COVID-19 patients through a systematic review and meta-analysis. This systematic review and meta-analysis were reported following 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 hub/PubMed, Scopus, ISI 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's 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 the Favipiravir group than in the 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 the 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.

The Saudi Critical Care Society practice guidelines on the management of COVID-19 in the ICU: Therapy section

“…Our search identified two systematic reviews and meta-analyses that summarized the results of RCTs on favipiravir in hospitalized COVID-19 patients [ 56 , 57 ]. The most recent preprint systematic review and meta-analysis included 9 RCTs (n = 827) comparing favipiravir to any other intervention; out of those, only 3 studies compared favipiravir to usual care or placebo.…”

Drug-Induced Liver Injury in COVID-19 Patients: A Systematic Review

“…A review on the safety and efficacy of FRP in COVID-19 patients revealed that there is not a significant difference in LFT changes in the FRP group compared to the comparison group (56). Consistently, a recent meta-analysis study reported FRP leads to non-significantly lower odds for adverse effects compared to placebo (57).…”

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“…In addition, a recent clinical study (N=80) with mild to moderate COVID-19 patients revealed that treatment with Favipiravir led to shorter viral clearance time (4 vs 11 days) and a significant improvement rate in chest imaging (CT) (91.43% vs. 62.22%), were observed [133]. Furthermore, a meta-analysis of nine clinical studies showed significant clinical improvement in the Favipiravir group versus the control group as reflected by viral clearance rate, requirement for oxygen therapy, ICU transfer, and reduced mortality [134]. Favipiravir is approved for COVID-19 in China, India, Japan, and Russia (Table 5)…”