Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

BackgroundNitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain.MethodsA multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days.ResultsOf the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38–1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21–3.43], p < 0.0001), time to hospital discharge (1.37 [1.11–1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64–0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed.ConclusionsNitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia.Clinical Trial RegistrationBrazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.

Efficacy and safety of nitazoxanide in treating SARS-CoV-2 infection: a systematic review and meta-analysis of blinded, placebo-controlled, randomized clinical trials

“…The search strategy yielded 1031 potentially relevant records. After screening of titles and abstracts and evaluation of completed trials retrieved from ClinicalTrials.gov, eight full-text articles were assessed for eligibility, and five [ 23 – 27 ] blinded, placebo-controlled RCTs were included in the meta-analysis. A flow diagram of the study selection process and specific reasons for exclusion are detailed in the supplement (eFig.…”

“…The studies were conducted in the USA, Puerto Rico, Brazil, and Argentina and included individuals with mild to moderate COVID-19 [ 24 – 27 ] or requiring supplemental oxygen therapy [ 23 ]. All trial protocols were registered on ClinicalTrials.gov, had a parallel design, and were classified as Phase 2 or Phase 3.…”

Efficacy and safety of nitazoxanide in treating SARS-CoV-2 infection: A systematic review and meta-analysis of blinded, placebo- controlled, randomized clinical trials

“…Studies have recommended the use of nitazoxanide for patients with COVID-19 in low-and middle-income countries due to its low cost, large availability, and safety. Individual results have shown that nitazoxanide can reduce the viral load during the rst week of treatment [19,20], the levels of some in ammatory mediators including CRP and D-dimer [17,21], the time for hospital discharge [17,21], and the time to sustained clinical response [18] in patients with mild to moderate COVID-19.…”

“…Search strategy yielded 1,031 potentially relevant records. After screening of titles and abstracts and evaluation of completed trials retrieved from ClinicalTrials.gov, eight full-text articles were assessed for eligibility and ve [17][18][19][20][21] blinded, placebo-controlled RCTs were included in the meta-analysis. A ow diagram of the study selection process and speci c reasons for exclusion are detailed in the Supplement (eFig.…”

“…The studies were conducted in the USA, Puerto Rico, Brazil, and Argentina and included individuals with mild to moderate COVID- 19 [18-21] or requiring supplemental oxygen therapy [17]. All trial protocols were registered on ClinicalTrials.gov, had a parallel design, and were classi ed as Phase 2 or Phase 3.…”