Abstract
Purpose: Nitazoxanide is a broad-spectrum antiparasitic that has been tested for COVID-19 due to its anti-inflammatory effects and in vitro antiviral activity. This study synthesized the best evidence on the efficacy and safety of nitazoxanide in COVID-19.
Methods: Searches for studies were performed in peer-reviewed and grey-literature from January 1, 2020 to May 23, 2022. The following elements were used to define eligibility criteria: (1) Population: individuals with COVID-19; (2) Intervention: nitazoxanide; (3) Comparison: placebo; (4) Outcomes: primary outcome was death, and secondary outcomes were viral load, positive RT-PCR status, serum biomarkers of inflammation, composite measure of disease progression (ICU admission or invasive mechanical ventilation), and any adverse events; (5) Study type: blinded, placebo-controlled, randomized clinical trials (RCTs). Treatment effects were reported as relative risk (RR) for dichotomous variables and standardized mean difference (SMD) for continuous variables with 95% confidence intervals (CI).
Results: Five blinded, placebo-controlled RCTs were included and enrolled individuals with mild or moderate SARS-CoV-2 infection. We found no difference between nitazoxanide and placebo in reducing viral load (SMD = – 0.16; 95% CI – 0.38 to 0.05) and the frequency of positive RTP-PCR results (RR = 0.92; 95% CI 0.81 to 1.06). In addition, there was no decreased risk for disease progression (RR = 0.63; 95% CI 0.38 to 1.04) and death (RR = 0.81; 95% CI 0.36 to 1.78) among patients receiving nitazoxanide. Patients with COVID-19 treated with nitazoxanide had decreased levels of white blood cells (SMD = – 0.15; 95% – 0.29 to – 0.02), lactate dehydrogenase (LDH) (SMD – 0.32; 95% – 0.52 to – 0.13), and D-dimer (SMD – 0.49; 95% CI – 0.68 to – 0.31) compared to placebo, but the magnitude of effect was considered small to moderate.
Conclusion: This systematic review showed no evidence of clinical benefits of the use of nitazoxanide to treat patients with mild or moderate COVID-19. In addition, we found a reduction in WBC, LDH, and D-dimer levels among nitazoxanide-treated patients, but the effect size was considered small to moderate.
Keywords: COVID-19; Meta-analysis; Nitazoxanide; SARS-CoV-2 infection.
【저자키워드】 COVID-19, Meta-analysis, SARS-CoV-2 infection., nitazoxanide, 【초록키워드】 Inflammation, randomized clinical trial, SARS-COV-2 infection, LDH, systematic review, risk, D-dimer, in vitro, antiviral activity, lactate dehydrogenase, antiparasitic, RCT, Moderate COVID-19, Disease progression, White blood cell, Viral load, Patient, ICU admission, death, Mild, Efficacy and safety, Placebo, WBC, moderate, patients, placebo-controlled, RCTs, positive RT-PCR, Evidence, D-dimer level, Invasive mechanical ventilation, Frequency, Primary outcome, standardized mean difference, 95% CI, 95% confidence interval, individual, no difference, clinical benefit, eligibility, secondary outcome, treat, effect size, anti-inflammatory effect, positive, element, Effect, SMD, continuous variable, enrolled, tested, performed, blinded, reported, addition, receiving, treated, were used, reducing, magnitude, to define, reduction in, peer-reviewed, dichotomous variable, serum biomarker, with COVID-19, 【제목키워드】 SARS-CoV-2, randomized clinical trial, systematic review, placebo-controlled, blinded,