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. 2021 Jul:37:100981.
doi: 10.1016/j.eclinm.2021.100981. Epub 2021 Jun 27.

Nitazoxanide superiority to placebo to treat moderate COVID-19 - A Pilot prove of concept randomized double-blind clinical trial

Vinicius Fontanesi Blum  1 , Sérgio Cimerman  2 , James R Hunter  1 , Paulo Tierno  3 , Acioly Lacerda  4 , Alexandre Soeiro  5 , Florentino Cardoso  6 , Nancy Cristina Bellei  1 , Juliana Maricato  1 , Nathalia Mantovani  1 , Marcella Vassao  1 , Danilo Dias  1 , Juliana Galinskas  1 , Luis Mário Ramos Janini  1 , Joanna Reis Santos-Oliveira  7 , Alda Maria Da-Cruz  8 , Ricardo Sobhie Diaz  1
Affiliations

Nitazoxanide superiority to placebo to treat moderate COVID-19 - A Pilot prove of concept randomized double-blind clinical trial

Vinicius Fontanesi Blum et al. EClinicalMedicine. 2021 Jul.

Erratum in

Abstract

Background: The absence of specific antivirals to treat COVID-19 leads to the repositioning of candidates' drugs. Nitazoxanide (NTZ) has a broad antiviral effect.

Methods: This was a randomized, double-blind pilot clinical trial comparing NTZ 600 mg BID versus Placebo for seven days among 50 individuals (25 each arm) with SARS-COV-2 RT-PCR+ (PCR) that were hospitalized with mild respiratory insufficiency from May 20th, 2020, to September 21st, 2020 (ClinicalTrials.gov NCT04348409). Clinical and virologic endpoints and inflammatory biomarkers were evaluated. A five-point scale for disease severity (SSD) was used.

Findings: Two patients died in the NTZ arm compared to 6 in the placebo arm (p = 0.564). NTZ was superior to placebo when considering SSD (p < 0001), the mean time for hospital discharge (6.6 vs. 14 days, p = 0.021), and negative PCR at day 21 (p = 0.035), whereas the placebo group presented more adverse events (p = 0.04). Among adverse events likely related to the study drug, 14 were detected in the NTZ group and 22 in placebo (p = 0.24). Among the 30 adverse events unlikely related, 21 occurred in the placebo group (p = 0.04). A decrease from baseline was higher in the NTZ group for d-Dimer (p = 0.001), US-RCP (p < 0.002), TNF (p < 0.038), IL-6 (p < 0.001), IL-8 (p = 0.014), HLA DR. on CD4+ T lymphocytes (p < 0.05), CD38 in CD4+ and CD8+ T (both p < 0.05), and CD38 and HLA-DR. on CD4+ (p < 0.01).

Interpretation: Compared to placebo in clinical and virologic outcomes and improvement of inflammatory outcomes, the superiority of NTZ warrants further investigation of this drug for moderate COVID-19 in larger clinical trials. A higher incidence of adverse events in the placebo arm might be attributed to COVID-19 related symptoms.

Keywords: COVID-19; Interleukins; Lymphocytes cell activation markers; Nitazoxanide; Randomized controlled clinical trial.

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Conflict of interest statement

VB exerts activities of clinical research at FQM Farmoquímica, sponsor of the study. AL reports grants from FQM, during the conduct of the study; personal fees from Daiicho Sankyo Brasil, Pfizer, Mantecorp Indústria Química e Farmacêutica, Libs Farmacêutica, Sanofi-Aventis; grants, personal fees and non-financial support from Janssen Pharmaceutical; personal fees and non-financial support from Cristalia Produtos Químicos e Farmacêuticos; grants and personal fees from Eli Lilly; grants from H. Lundbeck A/S, Servier Laboratories, Hoffman-La Roche, Forum Pharmaceuticals, Biophytis, Ganentech, Cellavita, Celltrion (outside the submitted work). JG, DD, JH, and NM report personal fees from FMQ during the conduct of the study. SC reports grants from FQM during the conduct of the study; grants from MERCK SHARP & DOME, NOVARTIS, ROCHE, ABBVIE, GILEAD, and PFIZER (outside the submitted work). Other authors do not have any conflict of interest to declare.

Figures

Fig. 1
Fig. 1
Screening and Randomization Patients admitted for hospitalization with mild/moderate hypothesis of COVID-19 were screened (73 patients), and 50 patients were randomized once RT-PCR for SARS-COV-2 was positive in the nasal and throat swabs (RT-PCR results available in the first 12 h of hospital admissions). Patients were allocated to receive Nitazoxanide (25) or placebo (25). Five patients did not receive 7-day treatment with allocated study interventions. From the Nitazoxanide group, one patient dyed on day 2 of the study, one patient received four doses of study drug and withdrew informed consent. Another patient was released from the hospital in good health conditions on day 5 of the study and was lost to follow-up. From the placebo group, one patient dyed on day two and another on day 4. Available data for all patients have been analyzed by the end of the study period.
Fig. 2
Fig. 2
Relative slopes for the two treatment groups' viral loads, Nitazoxanide (NTZ) and Placebo.
Fig. 3
Fig. 3
T cell activation status over time among the NTZ and Placebo groups. Peripheral blood mononuclear cells (PBMC) from patients of all groups were obtained by Ficoll-Hypaque gradient centrifugation. PBMC was thawed and used for immunophenotyping on Day 1, Day 10, and Day 21. The MFI of CD38+CD4+T cells (3A), HLA-DR.+CD4+T cells (3B), CD38+CD8+T cells (3C), HLA-DR.+CD8+T cells (3D), CD38+HLA-DR.+CD4+T cells (3E), and CD38+HLA-DR.+CD8+T cells (3F) are expressed as the median ± standard deviation. Placebo is represented in black dots, whereas Nitazoxanide is represented in green dots.
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References

    1. Valencia D.N. Brief Review on COVID-19: the 2020 pandemic caused by SARS-CoV-2. Cureus. 2020; 12. doi:10.7759/cureus.7386. - PMC - PubMed
    1. Rello J., Storti E., Belliato M., Serrano R. Clinical phenotypes of SARS-CoV-2: implications for clinicians and researchers. Eur Respir J. 2020;55 - PMC - PubMed
    1. Guan W., Ni Z., Hu Y. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382:1708–1720. - PMC - PubMed
    1. Zhang J., Dong X., Cao Y. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020;75:1730–1741. - PubMed
    1. Romagnoli S., Peris A., De Gaudio A.R., Geppetti P. SARS-CoV-2 and COVID-19: from the bench to the bedside. Physiological Reviews. 2020;100:1455–1466. - PMC - PubMed

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