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

Haoshuang Liu; Jingfeng Chen; Weihao Shao; Su Yan; Suying Ding

doi:10.2147/CLEP.S422386

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

Clin Epidemiol. 2023 Nov 1:15:1041-1053. doi: 10.2147/CLEP.S422386. eCollection 2023.

Authors

Haoshuang Liu^{1

2}, Jingfeng Chen^{1

2}, Weihao Shao³, Su Yan^{1

2}, Suying Ding^{1

2}

Affiliations

¹ Health Management Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
² College of Public Health, Zhengzhou University, Zhengzhou, 450001, People's Republic of China.
³ School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People's Republic of China.

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.

Keywords: COVID-19; efficacy; network meta-analysis; pharmacological intervention; safety.

Publication types

Review

Grants and 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.