Covid-19 living Data

Pharmacologic treatments for covid-19 patients

Hydroxychloroquine + Azithromycin vs Hydroxychloroquine

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

Outpatients

Forest plots
(last update: 2022-04-12)

Summary of findings
(last update: 2022-06-01)

Patient or population: COVID-19 patients
Setting: Worldwide
Intervention: Hydroxychloroquine + Azithromycin
Comparison: Hydroxychloroquine

Outcome	Relative effect (95% CI)	Absolute effect (95% CI)¹		Certainty of the Evidence (GRADE)
Clinical improvement D28	RR: 0.95 (0.65 - 1.40)	21 fewer per 1000 (from 148 fewer to 169 more)		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
1 trials Johnston C, 2021 148 participants		Hydroxychloroquine + Azithromycin 401 per 1,000 (275 - 592)	Hydroxychloroquine 423 per 1,000
Clinical improvement D60	Outcome not yet measured or reported
Hospitalisation or death	RR: 1.35 (0.44 - 4.20)	8 more per 1000 (from 13 fewer to 72 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 Johnston C, 2021; Omrani A, 2020 452 participants		Hydroxychloroquine + Azithromycin 30 per 1,000 (10 - 94)	Hydroxychloroquine 22 per 1,000
WHO progression score (level 7 or above) D28	Outcome not yet measured or reported
WHO progression score (level 7 or above) D60	Outcome not yet measured or reported
All-cause mortality D28	RR: ( - )	Zero events in both groups		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious no events in both groups and low number of participants
2 trials Johnston C, 2021; Omrani A, 2020 452 participants		Hydroxychloroquine + Azithromycin 0 per 1,000 ( - )	Hydroxychloroquine 0 per 1,000
All-cause mortality D60	Outcome not yet measured or reported
Viral negative conversion D7	RR: 0.86 (0.66 - 1.11)	39 fewer per 1000 (from 95 fewer to 31 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: Very serious due to very wide confidence interval consistent with the possibility for no effect and the possibility for harm and low number of participants
2 trials Johnston C, 2021; Omrani A, 2020 452 participants		Hydroxychloroquine + Azithromycin 239 per 1,000 (183 - 309)	Hydroxychloroquine 278 per 1,000
Adverse events	Outcome not yet measured or reported
Serious adverse events	RR: ( - )	Zero events in both groups		Low certainty Reasons to downgrade Risk of bias: Not serious 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 no events in both groups and low number of participants
1 trials Omrani A, 2020 304 participants		Hydroxychloroquine + Azithromycin 0 per 1,000 ( - )	Hydroxychloroquine 0 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: 2022-04-12)

Summary of findings
(last update: 2022-05-04)

Patient or population: COVID-19 patients
Setting: Worldwide
Intervention: Hydroxychloroquine + Azithromycin
Comparison: Hydroxychloroquine

Outcome	Relative effect (95% CI)	Absolute effect (95% CI)¹		Certainty of the Evidence (GRADE)
Clinical improvement D28	RR: 0.92 (0.74 - 1.16)	51 fewer per 1000 (from 167 fewer to 103 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level:some concerns due to deviation from intended intervention, outcome measurement and selection of reported results Inconsistency: Serious I²=72.10% Indirectness: Serious studies from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Serious due to wide confidence interval consistent with the possibility for harm and the possibility for no effect and low number of events
2 trials Cavalcanti AB, 2020; Furtado RHM, 2020 885 participants		Hydroxychloroquine + Azithromycin 591 per 1,000 (476 - 746)	Hydroxychloroquine 643 per 1,000
Clinical improvement D60	Outcome not yet measured or reported
WHO progression score (level 7 or above) D28	RR: 1.08 (0.90 - 1.30)	21 more per 1000 (from 26 fewer to 77 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns regarding deviations from intended interventions and selection of reported results Inconsistency: Not serious Indirectness: Serious studies from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Very serious due to wide confidence interval consistent with the possibility for harm and the possibility for no effect and low number of events
2 trials Cavalcanti AB, 2020; Furtado RHM, 2020 885 participants		Hydroxychloroquine + Azithromycin 278 per 1,000 (232 - 335)	Hydroxychloroquine 258 per 1,000
WHO progression score (level 7 or above) D60	Outcome not yet measured or reported
All-cause mortality D28	RR: 0.88 (0.44 - 1.76)	24 fewer per 1000 (from 113 fewer to 153 more)		Very low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Serious studies from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Very serious due to wide confidence interval consistent with the possibility for benefit and the possibility for harm and low number of participants
2 trials Cavalcanti AB, 2020; Furtado RHM, 2020 885 participants		Hydroxychloroquine + Azithromycin 178 per 1,000 (89 - 355)	Hydroxychloroquine 202 per 1,000
All-cause mortality D60	Outcome not yet measured or reported
Viral negative conversion D7	Outcome not yet measured or reported
Adverse events	RR: 1.13 (0.88 - 1.45)	44 more per 1000 (from 40 fewer to 151 more)		Low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns regarding deviation from intended intervention and outcome measurement 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: Serious due to wide confidence interval consistent with the possibility for no effect and the possibility for harm and low number of participants
1 trials Calvicanti AB, 2020 438 participants		Hydroxychloroquine + Azithromycin 378 per 1,000 (295 - 486)	Hydroxychloroquine 335 per 1,000
Serious adverse events	RR: 1.20 (0.95 - 1.51)	36 more per 1000 (from 9 fewer to 92 more)		Low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level:some concerns regarding deviation from intended intervention and outcome measurement Inconsistency: Not serious Indirectness: Not serious We presume that the adverse event rates, and the corresponding relative risks, is similar across diverse settings; therefore not downgraded for indirectness Imprecision: Serious due to wide confidence interval consistent with the possibility for no effect and the possibility for harm and low number of participants
2 trials Cavalcanti AB, 2020; Furtado RHM, 2020 885 participants		Hydroxychloroquine + Azithromycin 217 per 1,000 (172 - 273)	Hydroxychloroquine 181 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

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Permanent URL for this comparison: https://covid-nma.com/living_data/index.php?comparison=29

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Trial	Funding	Comparisons		Design	Participants	Sample size	Overall risk of bias Highest assessment	Full description
		Treatment 1	Treatment 2
NCT04354428 Johnston C, EClinicalMedicine, 2021 Full text Commentary Commentary Commentary	Public/non profit	Hydroxychloroquine sulphate+azithromycin Hydroxychloroquine+Placebo Hydroxychloroquine sulphate+azithromycin	Vitamin C+Placebo Vitamin C+Placebo Hydroxychloroquine+Placebo	RCT	Outpatients with confirmed COVID-19 (asymptomatic-mild) treated by 5 centers in the USA	N=231	Some concerns Details	Full description
NCT04349592 Q-PROTECT Omrani A, EClinicalMedicine, 2020 Full text Commentary	Public/non profit	Hydroxychloroquine+azithromycin Hydroxychloroquine Hydroxychloroquine+azithromycin	Placebo Placebo Hydroxychloroquine	RCT	Outpatients with confirmed COVID-19 (mild) treated by 2 centers in Qatar	N=456	Some concerns Details	Full description
NCT04321278 Furtado RHM, Lancet, 2020 Full text	Mixed	Azithromycin + Hydroxychloroquine	Hydroxychloroquine	RCT	Patients with suspected or confirmed COVID-19 (moderate-critical) admitted to 57 centers in Brazil	N=447	Some concerns Details	Full description
NCT04322123 Cavalcanti AB, N Engl J Med, 2020 Full text Commentary	Mixed	Hydroxychloroquine+Azithromycin Hydroxychloroquine Hydroxychloroquine	Standard care	RCT	Patients with suspected or confirmed COVID-19 (mild-moderate) admitted to 55 centers in Brazil	N=667	Some concerns Details	Full description