Covid-19 living Data

Pharmacologic treatments for covid-19 patients

Nitazoxanide vs Standard care/Placebo

This comparison will not be updated. Last search date 28 Feb, 2022.

Outpatients

Forest plots
(last update: 2022-08-18)

Summary of findings
(last update: 2022-08-30)

Patient or population: COVID-19 patients
Setting: Worldwide
Intervention: Nitazoxanide
Comparison: Standard care/Placebo

Outcome	Relative effect (95% CI)	Absolute effect (95% CI)¹		Certainty of the Evidence (GRADE)
Clinical improvement D28	RR: 0.92 (0.79 - 1.07)	49 fewer per 1000 (from 129 fewer to 43 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Serious despite a multicentre design this is a single study from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Serious due to low number of participants/events
1 trials Rocco PRM, 2020 475 participants		Nitazoxanide 567 per 1,000 (487 - 659)	Standard care/Placebo 616 per 1,000
Clinical improvement D60	Outcome not yet measured or reported
Hospitalisation or death	RR: 0.52 (0.10 - 2.69)	12 fewer per 1000 (from 23 fewer to 43 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
2 trials Rossignol JF, 2022; Rocco PRM, 2020 854 participants		Nitazoxanide 13 per 1,000 (3 - 68)	Standard care/Placebo 25 per 1,000
WHO progression score (level 7 or above) D28	RR: 2.99 (0.12 - 72.97)	Absolute effects were not calculated due to zero events in the control group		Very low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Serious despite a multicentre design this is a single study from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
2 trials Rocco PRM, 2020; Medhat M, 2022 625 participants		Nitazoxanide 0 per 1,000 (* - *)	Standard care/Placebo 0 per 1,000
WHO progression score (level 7 or above) D60	Outcome not yet measured or reported
All-cause mortality D28	RR: 5.30 (0.26 - 109.61)	Absolute effects were not calculated due to zero events in the control group		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
3 trials Rossignol JF, 2021; Rocco PRM, 2020; Medhat M, 2022 1004 participants		Nitazoxanide 0 per 1,000 (* - *)	Standard care/Placebo 0 per 1,000
All-cause mortality D60	Outcome not yet measured or reported
Viral negative conversion D7	RR: 1.76 (1.29 - 2.41)	135 more per 1000 (from 51 more to 250 more)		Low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level:some concerns regarding adequate randomisation, deviation from intended intervention, missing data and selection of the reported results Inconsistency: Not serious Indirectness: Not serious Imprecision: Serious due to low number of participants/events
2 trials Rocco PRM, 2020; Medhat M, 2022 542 participants		Nitazoxanide 312 per 1,000 (228 - 427)	Standard care/Placebo 177 per 1,000
Adverse events	RR: 0.93 (0.76 - 1.14)	22 fewer per 1000 (from 75 fewer to 44 more)		Low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns regarding missing data, and selection of the reported results Inconsistency: Not serious Indirectness: Not serious Imprecision: Serious due to low number of participants/events
2 trials Rossignol JF, 2022; Rocco PRM, 2020 854 participants		Nitazoxanide 291 per 1,000 (238 - 356)	Standard care/Placebo 313 per 1,000
Serious adverse events	RR: 0.30 (0.06 - 1.44)	11 fewer per 1000 (from 15 fewer to 7 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level:some concerns regarding missing data and selection of the reported results Inconsistency: Not serious Indirectness: Not serious Imprecision: Serious due to wide confidence interval consistent with the possibility for benefit and the possibility for no effect/trivial effect
2 trials Rocco PRM, 2020; Rossignol JF, 2021 854 participants		Nitazoxanide 5 per 1,000 (1 - 23)	Standard care/Placebo 16 per 1,000

¹The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Hospitalized patients

Forest plots
(last update: 2022-01-04)

Summary of findings
(last update: 2022-03-30)

Patient or population: COVID-19 patients
Setting: Worldwide
Intervention: Nitazoxanide
Comparison: Standard care/Placebo

Outcome	Relative effect (95% CI)	Absolute effect (95% CI)¹		Certainty of the Evidence (GRADE)
Clinical improvement D28	Outcome not yet measured or reported			2 studies were identified that assessed this outcome, but no results were reported.
Clinical improvement D60	Outcome not yet measured or reported
WHO progression score (level 7 or above) D28	RR: 0.33 (0.07 - 1.50)	161 fewer per 1000 (from 223 fewer to 120 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns regarding adequate randomization and deviation from intended intervention Inconsistency: Not serious Indirectness: Serious despite a multicentre design this is a single study from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
1 trials Blum VF, 2021 50 participants		Nitazoxanide 79 per 1,000 (17 - 360)	Standard care/Placebo 240 per 1,000	1 additional study was identified that assessed this outcome, but no results were reported.
WHO progression score (level 7 or above) D60	Outcome not yet measured or reported
All-cause mortality D28	RR: 0.35 (0.09 - 1.29)	120 fewer per 1000 (from 168 fewer to 53 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns regarding adequate randomization and deviation from intended intervention and high risk of bias due to missing data. Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious Imprecision downgraded by 2 level: due to wide confidence interval consistent with the possibility for benefit and the possibility for harm and very low number of events
2 trials Silva M, 2021; Blum VF, 2021 96 participants		Nitazoxanide 64 per 1,000 (17 - 238)	Standard care/Placebo 184 per 1,000
All-cause mortality D60	Outcome not yet measured or reported
Viral negative conversion D7	RR: 0.79 (0.41 - 1.50)	113 fewer per 1000 (from 318 fewer to 269 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level:some concerns or high risk regarding adequate randomization, deviations from intended interventions and missing data Inconsistency: Not serious Indirectness: Serious despite a multicentre design this is a single study from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
1 trials Silva M, 2021 46 participants		Nitazoxanide 425 per 1,000 (221 - 808)	Standard care/Placebo 538 per 1,000
Adverse events	RR: 0.62 (0.31 - 1.22)	198 fewer per 1000 (from 359 fewer to 114 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns regarding adequate randomization, deviations from intended intervention, outcome measurement and selection of reported results. Inconsistency: Not serious Indirectness: Not serious We presume that the adverse event rates and the corresponding relative risks, are similar across diverse settings, therefore not downgraded for indirectness Imprecision: Very serious due to wide confidence interval consistent with the possibility for benefit and the possibility for no effect and very low number of participants
1 trials Blum VF, 2021 50 participants		Nitazoxanide 322 per 1,000 (161 - 634)	Standard care/Placebo 520 per 1,000
Serious adverse events	Outcome not yet measured or reported

¹The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)

CI: Confidence interval; RR: Risk ratio

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click here for Outpatients
click here for Hospitalized patients

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Permanent URL for this comparison: https://covid-nma.com/living_data/index.php?comparison=118

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Trial	Funding	Comparisons		Design	Participants	Sample size	Overall risk of bias Highest assessment	Full description
		Treatment 1	Treatment 2
NCT04498936 Medhat M, Arab J Gastroenterol, 2022 Full text Commentary	Public/non profit	Sofosbuvir/ledipasvir Nitazoxanide Sofosbuvir/ledipasvir	Standard care Standard care Nitazoxanide	RCT	Outpatients and isolated patients with confirmed COVID-19 (mild-moderate) treated at 3 centers in Egypt.	N=220	Some concerns Details	Full description
NCT04486313 Rossignol JF, EClinicalMedicine, 2022 Full text Full text Full text Full text Commentary Commentary Commentary	Private	Nitazoxanide	Placebo	RCT	Outpatients with confirmed or suspected COVID-19 (mild, symptomatic) treated at 36 centers in Puerto Rico and USA.	N=379	Some concerns Details	Full description
NCT04463264 Silva M, medRxiv, 2021 Full text Commentary Commentary	Private	Nitazoxanide	Placebo	RCT	Outpatients and inpatients with confirmed COVID-19 (asymptomatic or symptomatic-mild) treated by or admitted to two centers in Argentina	N=46	High Details	Full description
NCT04348409 Blum VF, EClinicalMedicine, 2021 Full text Full text Commentary	Private	Nitazoxanide	Placebo	RCT	Patients with confirmed COVID-19 (mild/moderate) admitted to 6 centers in Brazil.	N=50	Some concerns Details	Full description
NCT04552483 Rocco PRM, Eur Respir J, 2020 Full text Commentary	Mixed	Nitazoxanide	Placebo	RCT	Outpatients with confirmed COVID-19 (mild) treated at 7 centers in Brazil	N=475	Some concerns Details	Full description