Nitazoxanide for COVID-19: real-time analysis of all 14 studies

Sofosbuvir/Ledipasvir in Combination or Nitazoxanide Alone are Safe and Efficient Treatments for COVID-19 Infection: A Randomized Controlled Trial for Repurposing antivirals

Medhat et al., Arab Journal of Gastroenterology, doi:10.1016/j.ajg.2022.04.005

RCT with 77 nitazoxanide, 70 sofosbuvir/ledipasvir, and 73 SOC patients in Egypt, showing faster viral clearance with nitazoxanide and with sofosbuvir/ledipasvir. There was no mortality or progression to severe COVID-19 or ICU admission. Nitazoxanide 500mg qid for 14 days. SOC included vitamin C and zinc.

risk of no viral clearance, 55.5% lower, HR 0.44, p = 0.02, treatment 77, control 73, Cox proportional hazards.

Medhat et al., 5/6/2022, Randomized Controlled Trial, Egypt, Africa, peer-reviewed, 20 authors, study period July 2020 - October 2021, trial NCT04498936.

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

Rocco et al., Frontiers in Medicine, doi:10.3389/fmed.2022.844728

RCT late stage patients with COVID-19 pneumonia, 202 treated with nitazoxanide and 203 placebo patients, showing improved recovery, but no significant difference in mortality.

risk of death, 4.9% higher, RR 1.05, p = 0.94, treatment 6 of 202 (3.0%), control 5 of 203 (2.5%), adjusted, OR converted to RR, multivariable, day 14.

risk of ICU admission, 30.5% lower, RR 0.69, p = 0.18, treatment 20 of 202 (9.9%), control 30 of 203 (14.8%), NNT 21, adjusted, OR converted to RR, multivariable, day 14.

risk of oxygen therapy, 39.7% lower, RR 0.60, p = 0.06, treatment 22 of 202 (10.9%), control 33 of 203 (16.3%), NNT 19, adjusted, OR converted to RR, multivariable, day 14.

time to improvement, 63.6% lower, HR 0.36, p < 0.001, treatment 202, control 203, Kaplan–Meier.

improvement, 34.2% better, OR 0.66, p = 0.14, treatment 202, control 203, adjusted, multivariable, day 14, RR approximated with OR.

time to discharge, 27.0% lower, HR 0.73, p = 0.004, treatment 202, control 203, Kaplan–Meier.

discharge, 8.3% lower, OR 0.92, p = 0.82, treatment 202, control 203, adjusted, multivariable, day 14, RR approximated with OR.

Rocco et al., 4/13/2022, Double Blind Randomized Controlled Trial, placebo-controlled, Brazil, South America, peer-reviewed, median age 56.0, 37 authors, study period 20 April, 2020 - 2 October, 2020, trial NCT04561219.

ANTICOV Trial Finds Nitazoxanide/Ciclesonide Drug Combination Does Not Reduce Hospitalisation Risk in Patients With Mild COVID-19

ANTICOV News (News)

RCT with 462 nitazoxanide/ciclesonide and 443 paracetamol patients, up to 7 days from onset, showing no significant difference in progression. Minimal details, with the primary mortality outcome and treatment delay not being reported. NCT04920838.

risk of progression, 187.7% higher, RR 2.88, p = 0.04, treatment 15 of 462 (3.2%), control 5 of 443 (1.1%), SpO2 ≤ 93% within 14 days.

Excluded in after exclusion results of meta analysis: minimal details provided.

ANTICOV et al., 2/28/2022, Randomized Controlled Trial, multiple countries, multiple regions, preprint, 1 author, this trial compares with another treatment - results may be better when compared to placebo, this trial uses multiple treatments in the treatment arm (combined with ciclesonide) - results of individual treatments may vary, trial NCT04920838.

The oral drug nitazoxanide restricts SARS-CoV-2 infection and attenuates disease pathogenesis in Syrian hamsters

Miorin et al., bioRxiv, doi:10.1101/2022.02.08.479634 (Preprint)

In Vitro study showing that nitazoxanide inhibits SARS-CoV-2 in H9, iAT2, Vero E6, Vero TMPRSS2, and Ace2-A549 cells.

Syrian hamster study showing improvements in SARS-CoV-2 related weight loss, inflammation, viral load, and lung synctia formation with nitazoxanide.

Miorin et al., 2/9/2022, preprint, 35 authors.

Efficacy and safety of nitazoxanide combined with ritonavir-boosted atazanavir for the treatment of mild to moderate COVID-19

Fowotade et al., medRxiv, doi:10.1101/2022.02.03.22270152 (Preprint)

Small RCT in Nigeria with 31 nitazoxanide and atazanavir/ritonavir patients, and 26 control patients, showing no significant differences with treatment. 4 treatment group patients discontinued treatment due to the size of the tablets. Time from onset is not provided, only time from diagnosis. NACOVID. 14-day course of nitazoxanide (1000 mg b.i.d.) and atazanavir/ritonavir (300/100 mg od). NCT04459286.

risk of no recovery, 11.4% higher, HR 1.11, p = 0.72, treatment 31, control 26, time to clinical improvement, Cox proportional hazards, primary outcome.

risk of no recovery, 86.9% higher, HR 1.87, p = 0.10, treatment 31, control 26, time to symptom resolution, Cox proportional hazards.

viral load, 5.2% lower, relative load 0.95, p = 0.92, treatment 31, control 26, viral load change from days 2 to 28.

Fowotade et al., 2/4/2022, Randomized Controlled Trial, Nigeria, Africa, preprint, 18 authors, study period 25 November, 2020 - 20 April, 2021, this trial uses multiple treatments in the treatment arm (combined with atazanavir/ritonavir) - results of individual treatments may vary, trial NCT04459286.

Treatment with hydroxychloroquine vs nitazoxanide in patients with COVID-19: brief report

Calderón et al., PAMJ - Clinical Medicine, doi:10.11604/pamj-cm.2021.7.15.30981

Planned RCT of HCQ vs. HCQ+nitazoxanide which was aborted due to the retracted Surgisphere paper. Authors retrospectively analyze a small set of HCQ vs. nitazoxanide patients (which were protocol deviations in the planned RCT), showing reduced hospitalization time and ICU admission with nitazoxanide.

risk of death, 68.2% lower, RR 0.32, p = 0.38, treatment 1 of 17 (5.9%), control 5 of 27 (18.5%), NNT 7.9.

risk of mechanical ventilation, 86.7% lower, RR 0.13, p = 0.15, treatment 0 of 17 (0.0%), control 4 of 27 (14.8%), NNT 6.8, relative risk is not 0 because of continuity correction due to zero events.

risk of ICU admission, 59.3% lower, RR 0.41, p < 0.001, treatment 0 of 17 (0.0%), control 16 of 27 (59.3%), NNT 1.7, adjusted.

hospitalization time, 51.8% lower, relative time 0.48, p = 0.006, treatment 17, control 27.

Calderón et al., 11/23/2021, retrospective, Mexico, North America, peer-reviewed, 7 authors, this trial compares with another treatment - results may be better when compared to placebo.

An open label, adaptive, phase 1 trial of high-dose oral nitazoxanide in healthy volunteers: an antiviral candidate for SARS-CoV-2

Walker et al., Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2463 (preprint 9/11/2021)

Phase I trial of high dose nitazoxanide, 1500mg twice daily, with 14 participants. Treatment was safe and well tolerated. PBPK predictions were confirmed on day 1 but with underprediction at day 5. Median Cmin was above the in vitro target concentration after the first dose and maintained throughout. NCT04746183.

Walker et al., 9/11/2021, peer-reviewed, 33 authors, trial NCT04746183.

Mantiene Hospital Mónica Pretelini bajo índice de muertes Covid de mujeres embarazadas

Calderón et al., News Report (News)

News report on the use of nitazoxanide for pregnant COVID-19 patients in a clinic in Mexico, reporting significant improvements in hospitalization and mortality compared to locations without treatment.

Calderón et al., 8/10/2021, preprint, 1 author.

Evolution of COVID-19 Pregnancies Treated With Nitazoxanide in a Third-Level Hospital

Enríquez López et al., Cureus, doi:10.7759/cureus.15002

Case study of 51 COVID-19 positive pregnant women in Mexico treated with nitazoxanide, showing much better survival compared to hospitals not using nitazoxanide.

Enríquez López et al., 5/13/2021, peer-reviewed, 10 authors.

A randomized double-blind placebo-controlled clinical trial of nitazoxanide for treatment of mild or moderate COVID-19

Rossignol et al., eClinicalMedicine, doi:10.1016/j.eclinm.2022.101310 (preprint 3/31/2021)

RCT with 184 outpatients treated with an extended release formulation of nitazoxanide, and 195 controls, showing lower hospitalization and progression to severe disease with treatment. There was one COVID-19 related death in the treatment arm. 600mg twice daily for five days. NCT04486313.

risk of death, 206.0% higher, RR 3.06, p = 0.49, treatment 1 of 184 (0.5%), control 0 of 195 (0.0%), continuity correction due to zero event, COVID-19 deaths.

risk of hospitalization, 78.8% lower, RR 0.21, p = 0.22, treatment 1 of 184 (0.5%), control 5 of 195 (2.6%), NNT 49.

risk of severe case, 84.9% lower, RR 0.15, p = 0.07, treatment 1 of 184 (0.5%), control 7 of 195 (3.6%), NNT 33.

risk of severe case, 83.9% lower, RR 0.16, p = 0.07, treatment 1 of 112 (0.9%), control 7 of 126 (5.6%), NNT 21, high-risk subgroup.

time to sustained recovery, 7.3% higher, relative time 1.07, p = 0.88, treatment 184, control 195, primary outcome.

Rossignol et al., 3/31/2021, Double Blind Randomized Controlled Trial, USA, North America, peer-reviewed, 5 authors, study period August 2020 - February 2021, average treatment delay 1.83 days, trial NCT04486313.

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

Silva et al., medRxiv, doi:10.1101/2021.03.03.21252509 (Preprint)

Small RCT with 23 nitazoxanide and 13 control patients showing significantly more patients achieved over 35% reduction in viral load from baseline. NCT04463264.

relative mean improvement in Ct, 26.5% better, RR 0.74, p = 0.36, treatment 23, control 13.

risk of viral load reduction < 35% at day 7, 38.3% lower, RR 0.62, p = 0.08, treatment 12 of 23 (52.2%), control 11 of 13 (84.6%), NNT 3.1.

Silva et al., 3/5/2021, Single Blind Randomized Controlled Trial, Argentina, South America, preprint, 11 authors, trial NCT04463264.

Effect of a combination of Nitazoxanide, Ribavirin and Ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-1

Elalfy et al., J. Med. Virol., doi:10.1002/jmv.26880

Non-randomized controlled trial with 62 mild and early moderate patients with home treatment with ivermectin + nitazoxanide + ribavirin + zinc, showing significantly faster viral clearance.

risk of no viral clearance, 86.9% lower, RR 0.13, p < 0.001, treatment 7 of 62 (11.3%), control 44 of 51 (86.3%), NNT 1.3, day 15.

risk of no viral clearance, 58.1% lower, RR 0.42, p < 0.001, treatment 26 of 62 (41.9%), control 51 of 51 (100.0%), NNT 1.7, day 7.

Elalfy et al., 2/16/2021, retrospective, Egypt, Africa, peer-reviewed, 15 authors, this trial uses multiple treatments in the treatment arm (combined with ivermectin, ribavirin, and zinc) - results of individual treatments may vary.

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

Blum et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100981 (preprint 1/22)

RCT with 25 nitazoxanide patients and 25 control patients, showing improved virological and clinical outcomes with treatment.

Authors also perform an in vitro study in Vero E6 cells showing 90% inhibition with 0.5µM, with no cytotoxicity. NCT04348409.

risk of death, 66.7% lower, RR 0.33, p = 0.25, treatment 2 of 25 (8.0%), control 6 of 25 (24.0%), NNT 6.3.

risk of mechanical ventilation, 62.5% lower, RR 0.38, p = 0.17, treatment 3 of 25 (12.0%), control 8 of 25 (32.0%), NNT 5.0.

relative severity scores, 20.2% better, RR 0.80, treatment 25, control 25.

hospitalization time, 55.7% lower, relative time 0.44, p = 0.02, treatment 25, control 25.

risk of no viral clearance, 89.8% lower, RR 0.10, p = 0.03, treatment 0 of 23 (0.0%), control 4 of 19 (21.1%), NNT 4.8, relative risk is not 0 because of continuity correction due to zero events, day 21.

Blum et al., 1/22/2021, Double Blind Randomized Controlled Trial, Brazil, South America, peer-reviewed, 17 authors, trial NCT04348409.

Early COVID-19 Therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in Outpatient Settings Significantly Improved COVID-19 outcomes compared to Known outcomes in untreated patients

Cadegiani et al., New Microbes and New Infections, doi:10.1016/j.nmni.2021.100915 (preprint 11/4/2020)

Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, even for those outcomes not influenced by placebo effect, at least when combined with azithromycin, and vitamin C, D and zinc in the majority of the cases. 585 patients with mean treatment delay 2.9 days. There was no hospitalization, mechanical ventilation, or mortality with treatment. Control group 1 was a retrospectively obtained group of untreated patients of the same population.

risk of death, 87.8% lower, RR 0.12, p = 0.08, treatment 0 of 357 (0.0%), control 2 of 137 (1.5%), NNT 68, relative risk is not 0 because of continuity correction due to zero events, control group 1.

risk of mechanical ventilation, 97.0% lower, RR 0.03, p < 0.001, treatment 0 of 357 (0.0%), control 9 of 137 (6.6%), NNT 15, relative risk is not 0 because of continuity correction due to zero events, control group 1.

risk of hospitalization, 99.0% lower, RR 0.01, p < 0.001, treatment 0 of 357 (0.0%), control 27 of 137 (19.7%), NNT 5.1, relative risk is not 0 because of continuity correction due to zero events, control group 1.

Cadegiani et al., 11/4/2020, prospective, Brazil, South America, peer-reviewed, 4 authors, average treatment delay 2.9 days.

Early use of nitazoxanide in mild Covid-19 disease: randomized, placebo-controlled trial (preprint 10/23)

Rocco et al., European Respiratory Journal, doi:10.1183/13993003.03725-2020 (preprint 10/23/20)

RCT 392 patients, median treatment delay 5 days, showing improved viral recovery at 5 days. Symptom recovery was no different at 5 days, and the treatment arm had two ICU admissions compared to zero for control. There were no serious adverse events.

risk of ICU admission, 404.1% higher, RR 5.04, p = 0.24, treatment 2 of 194 (1.0%), control 0 of 198 (0.0%), continuity correction due to zero event, table S3.

risk of hospitalization, 2.1% higher, RR 1.02, p = 1.00, treatment 5 of 194 (2.6%), control 5 of 198 (2.5%), table S3.

risk of no recovery, 15.8% higher, RR 1.16, p = 0.37, treatment 59 of 194 (30.4%), control 52 of 198 (26.3%), day 5.

relative viral load, 12.1% better, RR 0.88, p = 0.006, treatment 194, control 198, day 5.

risk of no viral clearance, 14.3% lower, RR 0.86, p = 0.009, treatment 136 of 194 (70.1%), control 162 of 198 (81.8%), NNT 8.5, day 5.

Rocco et al., 10/23/2020, Randomized Controlled Trial, Brazil, South America, peer-reviewed, 29 authors, average treatment delay 5.0 days.

Antiandrogens	(meta)	Lactoferrin	(meta)
Aspirin	(meta)	Melatonin	(meta)
Bamlaniv../e..	(meta)	Metformin	(meta)
Bebtelovimab	(meta)	Molnupiravir	(meta)
Bromhexine	(meta)	N-acetylcys..	(meta)
Budesonide	(meta)	Nigella Sativa	(meta)
Cannabidiol	(meta)	Nitazoxanide	(meta)
Casirivimab/i..	(meta)	Paxlovid	(meta)
Colchicine	(meta)	Peg.. Lambda	(meta)
Conv. Plasma	(meta)	Povidone-Iod..	(meta)
Curcumin	(meta)	Probiotics	(meta)
Diet	(meta)	Proxalutamide	(meta)
Ensitrelvir	(meta)	Quercetin	(meta)
Ensovibep	(meta)	Remdesivir	(meta)
Exercise	(meta)	Sleep	(meta)
Famotidine	(meta)	Sotrovimab	(meta)
Favipiravir	(meta)	Tixagev../c..	(meta)
Fluvoxamine	(meta)	Vitamin A	(meta)
Hydroxychlor..	(meta)	Vitamin C	(meta)
Iota-carragee..	(meta)	Vitamin D	(meta)
Ivermectin	(meta)	Zinc	(meta)

Other Treatments		Global Adoption