Covid-19 living Data

Pharmacologic treatments for covid-19 patients

Hydroxychloroquine + Azithromycin vs Standard care/Placebo

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

Outpatients

Forest plots
(last update: 2021-09-24)

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

Patient or population: COVID-19 patients
Setting: Worldwide
Intervention: Hydroxychloroquine + Azithromycin
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
Clinical improvement D60	Outcome not yet measured or reported
Hospitalisation or death	RR: 1.19 (0.34 - 4.17)	4 more per 1000 (from 14 fewer to 65 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 Rodrigues C, 2021; Omrani A, 2020 388 participants		Hydroxychloroquine + Azithromycin 25 per 1,000 (7 - 86)	Standard care/Placebo 21 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 Rodrigues C, 2021; Omrani A, 2020 388 participants		Hydroxychloroquine + Azithromycin 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: 0.95 (0.64 - 1.43)	9 fewer per 1000 (from 65 fewer to 78 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 Rodrigues C, 2021; Omrani A, 2020 388 participants		Hydroxychloroquine + Azithromycin 171 per 1,000 (115 - 258)	Standard care/Placebo 180 per 1,000
Adverse events	Outcome not yet measured or reported			1 study was identified that assessed this outcome, but no results were reported.
Serious adverse events	RR: 3.00 (0.13 - 71.61)	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
2 trials Rodrigues C, 2021; Omrani A, 2020 388 participants		Hydroxychloroquine + Azithromycin 0 per 1,000 ( - )	Standard care/Placebo 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: 2021-06-24)

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

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

Outcome	Relative effect (95% CI)	Absolute effect (95% CI)¹		Certainty of the Evidence (GRADE)
Clinical improvement D28	RR: 0.99 (0.93 - 1.06)	9 fewer per 1000 (from 60 fewer to 51 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 Imprecision: Serious due to low number of participants and events
2 trials Calvalcanti AB, 2020; Sivapalan P, 2021 563 participants		Hydroxychloroquine + Azithromycin 848 per 1,000 (796 - 908)	Standard care/Placebo 856 per 1,000
Clinical improvement D60	Outcome not yet measured or reported
WHO progression score (level 7 or above) D28	RR: 1.09 (0.56 - 2.11)	5 more per 1000 (from 25 fewer to 62 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious due to wide confidence interval consistent with the possibility for benefit and the possibility for harm and low number of participants and events
2 trials Cavalcanti AB, 2020; Sivapalan P, 2021 563 participants		Hydroxychloroquine + Azithromycin 61 per 1,000 (31 - 118)	Standard care/Placebo 56 per 1,000
WHO progression score (level 7 or above) D60	Outcome not yet measured or reported
All-cause mortality D28	RR: 0.51 (0.16 - 1.67)	14 fewer per 1000 (from 24 fewer to 19 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious due to wide confidence interval consistent with the possibility for benefit and the possibility for harm and low number of participants and events
2 trials Cavalcanti AB, 2020; Sivapalan P, 2021 563 participants		Hydroxychloroquine + Azithromycin 14 per 1,000 (4 - 47)	Standard care/Placebo 28 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: 1.42 (1.08 - 1.87)	112 more per 1000 (from 21 more to 232 more)		Low certainty Reasons to downgrade Risk of bias: Serious due to 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 low number of participants and events
1 trials Cavalcanti AB, 2020 446 participants		Hydroxychloroquine + Azithromycin 378 per 1,000 (288 - 498)	Standard care/Placebo 266 per 1,000
Serious adverse events	RR: 1.06 (0.22 - 5.17)	1 more per 1000 (from 10 fewer to 55 more)		Very low certainty Reasons to downgrade Risk of bias: Serious due to 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: Very serious due to wide confidence interval consistent with the possibility for benefit and the possibility for harm and low number of participants and events
1 trials Cavalcanti AB, 2020 446 participants		Hydroxychloroquine + Azithromycin 14 per 1,000 (3 - 68)	Standard care/Placebo 13 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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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=33

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Trial	Funding	Comparisons		Design	Participants	Sample size	Overall risk of bias Highest assessment	Full description
		Treatment 1	Treatment 2
RBR-95yjmq Rodrigues C, Int J Antimicrob Age, 2021 Full text Commentary	Private	Hydroxychloroquine + Azithromycin	Placebo	RCT	Outpatients with confirmed COIVD-19 (symptomatic, mild) treated by a single center in Brazil	N=84	Some concerns Details	Full description
NCT04322396, EudraCT 2020-001198-55 ProPAC-COVID Sivapalan P, Eur Respir J, 2021 Full text Commentary	Mixed	Hydroxychloroquine + Azithromycin	Placebo	RCT	Patients with confirmed COVID-19 (mild-severe) admitted to 6 centers in Denmark	N=117	Low 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
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