Efficacy of Nitazoxanide in reducing the viral load in COVID-19 patients. Randomized, placebo-controlled, single-blinded, parallel group, pilot study.

Abstract

The fast spread of COVID-19 has overcrowded Public Health Systems facilities in major countries due to the large number of seriously ill patients, particularly those requiring admission to intensive care units. Reducing viral load, along with other recommended epidemiological measures, such as social distancing and home confinement, can in time significantly help to reduce the infection R0 (Basic Reproductive Rate) and then mitigate disease burden. Early negativization or otherwise reduction of the viral load can potentially diminish disease severity, resulting in a better-controlled public health response, avoiding collapse of healthcare systems. Nitazoxanide, a widely used thiazolide approved by the FDA as an antiparasitic drug, also approved in Brazil for Norovirus and Rotavirus treatments, has an excellent safety record for a variety of indications. Nitazoxanide exhibits activity in vitro against MERS-CoV and other coronaviruses; and a specific antiviral effect (in micro molar doses) against SARS-CoV-2. The objective of this study was to evaluate the efficacy and safety of Nitazoxanide in reducing the SARS-COV 2 viral load within 7 days of treatment in respiratory samples from COVID-19-infected patients with mild to moderate disease, compared to placebo. An interim analysis showed that the ratio of patients with a viral load reduction ≥ 35% from baseline up to day 7 of treatment was significantly greater for Nitazoxanide compared to placebo (47.8% vs. 15.4%; Δ 34.6%; 95% CI: 64.7; 4.6: p = 0.037).

Strategies for drug repurposing against coronavirus targets

“…This potent in vitro activity is also seen against SARS-CoV-2 infected Vero E6 cells (2.12 μM EC 50 ; 35.53 μM IC 50 ), recommending further evaluation of nitazoxanide anti-CoV effects in vivo (M. Wang et al, 2020 ). Clinical studies of nitazoxanide treatment against COVID-19 do not illustrate convincing effectiveness ( Mendieta Zerón et al, 2021 ; Rocco et al, 2021 ; Silva et al, 2021 ).…”

Current status of therapeutic alternatives for COVID-19: A narrative review

“…Other investigated antiviral agents Although many potential antiviral agents have been investigated so far in RCTs, including darunavir/cobicistat, umifenovir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, ribavirin, nitazoxanide, and various interferon-based regimens, these studies have serious limitations [29,[54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69]. Until the results of ongoing trials evaluating these agents are available, the use of these drugs for the treatment of COVID-19 should be limited to randomized controlled trials.…”

Evidence of the Clinical Efficacy of Antiviral Agents against SARS-CoV-2

“…The mechanism may vary from virus to virus. NTZ inhibited SARS-CoV-2 by 90% in-vitro, [49] and showed promising efficacy in several parameters, including significantly reducing SARS-CoV-2 viral loads, [49][50][51][52] and immune markers [49] (Table 5). It has also shown efficacy in reducing hospitalization and disease progression, 48] and potential to treat COVID-19 symptoms [51].…”

“…NTZ inhibited SARS-CoV-2 by 90% in-vitro, [49] and showed promising efficacy in several parameters, including significantly reducing SARS-CoV-2 viral loads, [49][50][51][52] and immune markers [49] (Table 5). It has also shown efficacy in reducing hospitalization and disease progression, 48] and potential to treat COVID-19 symptoms [51]. Studies suggest that NTZ provides more clinical benefits, including reducing viral loads, time to recovery, and hospitalization, compared to placebo [52].…”