Favipiravir for the treatment of patients with COVID-19: a systematic review and meta-analysis

Abstract Background Favipiravir possesses high utility for treating patients with COVID-19. However, research examining the efficacy and safety of favipiravir for patients with COVID-19 is limited. Methods We conducted a systematic review of published studies reporting the efficacy of favipiravir against COVID-19. Two investigators independently searched PubMed, the Cochrane Database of Systematic Reviews, MedRxiv, and ClinicalTrials.gov (inception to September 2020) to identify eligible studies. A meta-analysis was performed to measure viral clearance and clinical improvement as the primary outcomes. Results Among 11 eligible studies, 5 included a comparator group. Comparing to the comparator group, the favipiravir group exhibited significantly better viral clearance on day 7 after the initiation of treatment (odds ratio [OR] = 2.49, 95% confidence interval [CI] = 1.19–5.22), whereas no difference was noted on day 14 (OR = 2.19, 95% CI = 0.69–6.95). Although clinical improvement was significantly better in the favipiravir group on both days 7 and 14, the improvement was better on day 14 (OR = 3.03, 95% CI = 1.17–7.80) than on day 7 (OR = 1.60, 95% CI = 1.03–2.49). The estimated proportions of patients with viral clearance in the favipiravir arm on days 7 and 14 were 65.42 and 88.9%, respectively, versus 43.42 and 78.79%, respectively, in the comparator group. The estimated proportions of patients with clinical improvement on days 7 and 14 in the favipiravir group were 54.33 and 84.63%, respectively, compared with 34.40 and 65.77%, respectively, in the comparator group. Conclusions Favipiravir induces viral clearance by 7 days and contributes to clinical improvement within 14 days. The results indicated that favipiravir has strong possibility for treating COVID-19, especially in patients with mild-to-moderate illness. Additional well-designed studies, including examinations of the dose and duration of treatment, are crucial for reaching definitive conclusions.

Download Full-text

Factors Affecting the Apparent Efficacy and Safety of Tissue Plasminogen Activator in Thrombotic Occlusion Models of Stroke: Systematic Review and Meta-Analysis

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2010.116 ◽

2010 ◽

Vol 30 (12) ◽

pp. 1905-1913 ◽

Cited By ~ 79

Author(s):

Emily S Sena ◽

Catherine L Briscoe ◽

David W Howells ◽

Geoffrey A Donnan ◽

Peter AG Sandercock ◽

...

Keyword(s):

Systematic Review ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Odds Ratio ◽

Infarct Volume ◽

Meta Analysis ◽

Efficacy And Safety ◽

Thrombotic Occlusion ◽

Tissue Plasminogen ◽

The Impact

Thrombolysis with recombinant tissue plasminogen activator (rtPA) improves outcome in animal models of stroke and in clinical trial, but is associated with increased intracranial hemorrhage. Here, we explore the impact of biologic and experimental design factors on efficacy and bleeding. We conducted a systematic review of studies describing the effect of tPA in thrombotic occlusion models of ischemic stroke followed by random effects meta-analysis, meta-regression, and trim and fill. We identified 202, 66, 128, and 54 comparisons reporting infarct volume, neurobehavioral score, hemorrhage, and mortality, respectively. The rtPA reduced infarct volume by 25.2% (95% confidence interval=21.8 to 28.6, 3388 animals), improved neurobehavioral score by 18.0% (12.6% to 23.3%, n=1243), increased the risk of hemorrhage (odds ratio=1.71, 1.42 to 2.07, n=2833) and had no significant effect on mortality (odds ratio=0.82, 0.62 to 1.08, n=1274). There was an absolute reduction in efficacy of 1.1% (0.7% to 1.4%) for every 10 minutes delay to treatment. Cumulative meta-analysis showed that the estimate of efficacy fell as more data became available. Publication bias inflated efficacy by 5.1% (infarct volume) and 8.1% (neurobehavioral score). This data set was large enough to be adequately powered to estimate with precision the impact of biologic and experimental factors on the efficacy and safety of rtPA.

Download Full-text

Favipiravir versus other antiviral or standard of care for COVID-19 treatment: a rapid systematic review and meta-analysis

Virology Journal ◽

10.1186/s12985-020-01412-z ◽

2020 ◽

Vol 17 (1) ◽

Cited By ~ 6

Author(s):

Dhan Bahadur Shrestha ◽

Pravash Budhathoki ◽

Sitaram Khadka ◽

Prajwol Bikram Shah ◽

Nisheem Pokharel ◽

...

Keyword(s):

Systematic Review ◽

Adverse Effects ◽

Clinical Improvement ◽

Rna Virus ◽

Meta Analysis ◽

Standard Of Care ◽

Viral Clearance ◽

Control Group ◽

Quantitative Synthesis ◽

Oxygen Requirements

Abstract Background The COVID-19 causing coronavirus is an enveloped RNA virus that utilizes an enzyme RNA dependent RNA polymerase for its replication. Favipiravir (FVP) triphosphate, a purine nucleoside analog, inhibits that enzyme. We have conducted this systematic review and meta-analysis on efficacy and safety of the drug FVP as a treatment for COVID-19. Methods Databases like Pubmed, Pubmed Central, Scopus, Embase, Google Scholar, preprint sites, and clinicaltirals.gov were searched. The studies with the standard of care (SOC) and FVP as a treatment drug were considered as the treatment group and the SOC with other antivirals and supportive care as the control group. Quantitative synthesis was done using RevMan 5.4. Clinical improvement, negative conversion of reverse transcription-polymerase chain reaction (RT-PCR), adverse effects, and oxygen requirements were studied. Results We identified a total of 1798 studies after searching the electronic databases. Nine in the qualitative studies and four studies in the quantitative synthesis met the criteria. There was a significant clinical improvement in the FVP group on the 14th day compared to the control group (RR 1.29, 1.08–1.54). Clinical deterioration rates were less likely in the FVP group though statistically not significant (OR 0.59, 95% CI 0.30–1.14) at the endpoint of study (7–15 days). The meta-analysis showed no significant differences between the two groups on viral clearance (day 14: RR 1.06, 95% CI 0.84–1.33), non-invasive ventilation or oxygen requirement (OR 0.76, 95% CI 0.42–1.39), and adverse effects (OR 0.69, 0.13–3.57). There are 31 randomized controlled trials (RCTs) registered in different parts of the world focusing FVP for COVID-19 treatment. Conclusion There is a significant clinical and radiological improvement following treatment with FVP in comparison to the standard of care with no significant differences on viral clearance, oxygen support requirement and side effect profiles.

Download Full-text

Outcomes following immunotherapy re-challenge after immune-related adverse event: systematic review and meta-analysis

Immunotherapy ◽

10.2217/imt-2020-0103 ◽

2020 ◽

Vol 12 (16) ◽

pp. 1183-1193

Author(s):

Robin Park ◽

Laercio Lopes ◽

Anwaar Saeed

Keyword(s):

Systematic Review ◽

Immune Checkpoint ◽

Odds Ratio ◽

Immune Checkpoint Inhibitors ◽

Response Rate ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Objective Response ◽

Cochrane Database ◽

Grade 3

Background: Given the inconclusive evidence behind the safety and efficacy of immune checkpoint inhibitors re-challenge, herein, we have conducted a systematic review and meta-analysis to synthesize available data. Results/methodology: PubMed, Embase, Cochrane Database, and ASCO and ESMO were searched for studies published from conception to March 2020. Pooled incidence of recurrent immune-related adverse events (irAEs), objective response rates, and odds ratios for irAEs at initial versus re-treatment were calculated. Overall, 437 patients (ten studies) were included. Incidence of any grade, grade 3/4, and steroid-requiring recurrent irAEs were 47%, 13.2%, and 26% respectively. Objective response rate in previous non-responders was 12.5% (5.8–24.8%). Odds ratio for severe irAEs was 0.28 (0.11–0.72) and steroid-requiring irAEs 0.19 (0.06–0.56). Discussion/conclusion: This analysis suggests that immune checkpoint inhibitors re-challenge is safe and potentially efficacious.

Download Full-text

Warming Acupuncture in the Treatment of Cervical Spondylotic Radiculopathy: A Systematic Review and Meta-analysis

Acupuncture & Electro-Therapeutics Research ◽

10.3727/036012921x16273277361795 ◽

2021 ◽

Author(s):

Wang Zuqing ◽

Li Yan

Keyword(s):

Systematic Review ◽

Odds Ratio ◽

Meta Analysis ◽

Effective Rate ◽

Risk Of Bias ◽

Cochrane Library ◽

Efficacy And Safety ◽

Vas Score ◽

Cervical Spondylotic Radiculopathy ◽

The Cochrane Library

Background: Warming acupuncture (WA) is widely used in the management of Cervical spondylotic radiculopathy (CSR)in China and obtains desirable efficacy. Therefore, the aim of this study is to systematically assess the efficacy and safety whether using WA alone or combined with traditional Chinese medicine (TCM) therapy for the treatment of CSR. Methods: PubMed, EMBASE, Sinomed, the Cochrane Library, CNKI, VIP and Wangfang databases were searched from their inception through 30 September 2020. All the retrieved records were screened or excluded based on the criteria that were pre-established, and the results that meet the criteria were assessed by the Cochrane risk of bias tool and Meta-analysis was conducted by using RevMan5.3 software. Results: Fourteen RCTs (1021patients) were included in the meta-analysis. The effective rate of WA alone or combination with TCM therapy was analyzed in comparison with the treatment of regular therapy. The results indicated that compared with regular therapy, WA alone or in combination with TCM therapy increased clinical effective rate (Odds ratio (OR)=4.43,95%CI 2.85 to 6.90, P<0.01). Additionally decreased VAS score (mean difference (MD)=-1.21,95%CI -1.68 to -0.73, P<0.01), PPI (MD=-1.34, 95% CI -2.08 to -0.61) and PRI (MD=-0.55,95% CI -0.72 to -0.37, P<0.001). However, adverse events of WA were not specially reported in all studies. Conclusions: WA as the main treatment for CSR can improve the clinical effective rate and reduce the level of VAS score, PPI and PRI. Further research is needed to determine the effectiveness of WA for CSR treatment, rigorously and unambiguously.

Download Full-text