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REVIEW

Efficacy and Safety of Novel Oral Antivirals in Hospitalized COVID-19 Patients: A Network Meta-Analysis of Randomized Clinical Trials

ORCID Icon, , ORCID Icon, & ORCID Icon
Pages 1041-1053 | Received 09 Jun 2023, Accepted 26 Sep 2023, Published online: 01 Nov 2023
 

Abstract

Objective

Numerous pharmacological interventions are now under investigation for the treatment of the 2019 coronavirus pandemic (COVID-19), and the evidence is rapidly evolving. Our aim is to evaluate the comparative efficacy and safety of these drugs.

Methods

We searched for randomized clinical trials (RCTs) on the efficacy and safety of novel oral antivirals for the treatment of hospitalized COVID-19 patients until November 30, 2022, including baricitinib, ivermectin (IVM), favipiravir (FVP), chloroquine (CQ), lopinavir and ritonavir (LPV/RTV), hydroxychloroquine (HCQ), and hydroxychloroquine plus azithromycin (HCQ+AZT). The main outcomes of this network meta-analysis (NMA) were in-hospital mortality, adverse event (AE), recovery time, and improvement in peripheral capillary oxygen saturation (SpO2). For dichotomous results, the odds ratio (OR) was used, and the 95% confidence interval (CI) was determined. We also used meta-regression to explore whether different treatments affected efficacy and safety. STATA 15.0 was used to conduct the NMA. The research protocol was registered with PROSPERO (#CRD 42023415743).

Results

Thirty-six RCTs, with 33,555 hospitalized COVID-19 patients, were included in this analysis. First, we compared the efficacy of different novel oral antivirals. Baricitinib (OR 0.56, 95% CI: 0.35 to 0.90) showed the highest probability of being the optimal probiotic species in reducing in-hospital mortality and suggested that none of the interventions reduced AE better than placebo. In terms of safety outcomes, IVM ranked first in improving the recovery time of hospitalized COVID-19 patients (mean difference (MD) −1.36, 95% CI: −2.32 to −0.39). In addition, patients were most likely to increase SpO2 (OR 1.77, 95% CI: 0.09 to 3.45). The meta-regression revealed no significant differences between participants using different novel oral antivirals in all outcomes in hospitalized COVID-19 patients.

Conclusion

Currently, baricitinib has reduced in-hospital mortality in hospitalized COVID-19 patients, with moderate certainty of evidence. IVM appeared to be a safer option than placebo in improving recovery time, while FVP was associated with increased SpO2 safety outcomes. These preliminary evidence-based observations should guide clinical practice until more data are made public.

Acknowledgments

We thank all the reviewers for their assistance and support.

Author Contributions

All authors have made significant contributions to the reported work, whether in conception, study design, execution, data acquisition, analysis, and interpretation, or in all of these areas; participated in the drafting, revision, or critical review of the article; gave final approval to the version to be published; agreed on the journal to which the article was submitted; and agreed to be responsible for all aspects of the work.

Disclosure

The authors declare that they have no competing interests in this work.

Additional information

Funding

This research was supported and funded by the Collaborative Innovation Project of Zhengzhou City (XTCX2023006) and the Nursing Team Project of the First Affiliated Hospital of Zhengzhou University (HLKY2023005). Funders had no role in designing, collecting, and analyzing data, deciding to publish, or preparing the manuscript.