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Vania dos Santos Nunes Nogueira
Departamento de Clínica Médica – FMB – UNESP Avenida Professor Mário Rubens Guimarães Montenegro s/n, Bairro UNESP, Campus Botucatu, Botucatu-SP 18618-687, Brazil
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9316-4167
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Despite the expectations regarding the effectiveness of chloroquine (CQ) and hydroxychloroquine (HCQ) for coronavirus disease (COVID-19) management, concerns about their adverse events have remained.
Objectives: The objective of this systematic review was to evaluate the safety of CQ and HCQ from malarial and non-malarial randomized clinical trials (RCTs).
Methods: The primary outcomes were the frequencies of serious adverse events (SAEs), retinopathy, and cardiac complications. Search strategies were applied to MEDLINE, EMBASE, LILACS, CENTRAL, Scopus, and Trip databases. We used random-effects model to pool results across studies and Peto one-step odds ratio (OR) for event rates below 1 %. Both-armed zero-event studies were excluded from the meta-analyses. We used the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate the certainty of evidence.
Results: Ninety-two RCTs were included. We found no significant difference between CQ/HCQ and control (placebo or non-CQ/HCQ) in the frequency of SAEs (OR: 0.98, 95 % confidence interval [CI]: 0.71–1.36, 25 trials, 11,605 participants, moderate certainty of evidence). No clear relationship was observed between CQ/HCQ and retinopathy (OR: 1,63, 95 % CI: -0.4–6.57, 5 trials, 344 participants, very low certainty of evidence). There was a low certainty of evidence of the effect of CQ/HCQ versus control on cardiac complications (Relative risk: 1.48, 95 % CI: 1.1–1.98, 8 trials, 5,970 participants).
Conclusions: CQ and HCQ might be safe, with low frequency of SAEs on malarial and non-malarial conditions. No clear effect of their use on the incidence of retinopathy and cardiac complications was observed.
The protocol for this systematic review was registered with PROSPERO (registration number: CRD42020177818)
Keywords
chloroquine, hydroxychloroquine, COVID-19, systematic review, meta-analysis
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CURRENT STATUS: Under Review
Version 1
Posted 14 Sep, 2020
No community comments so far
Editorial decision: Major revision
On 08 Apr, 2021
Review #4 received
Received 05 Apr, 2021
Review #3 received
Received 05 Apr, 2021
Review #1 received
Received 11 Mar, 2021
Reviewer #4 agreed
On 09 Mar, 2021
Reviewer #3 agreed
On 06 Mar, 2021
Reviewer #2 agreed
On 06 Mar, 2021
Review #2 received
Received 06 Mar, 2021
Reviewer #1 agreed
On 27 Feb, 2021
Reviewers invited
Invitations sent on 24 Feb, 2021
Editor assigned
On 30 Sep, 2020
Editor invited
On 29 Sep, 2020
Submission checks complete
On 10 Sep, 2020
First submitted
On 09 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Internal Medicine
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This preprint is under consideration at Systematic Reviews. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Vania dos Santos Nunes Nogueira
Departamento de Clínica Médica – FMB – UNESP Avenida Professor Mário Rubens Guimarães Montenegro s/n, Bairro UNESP, Campus Botucatu, Botucatu-SP 18618-687, Brazil
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9316-4167
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 14 Sep, 2020
No community comments so far
Editorial decision: Major revision
On 08 Apr, 2021
Review #4 received
Received 05 Apr, 2021
Review #3 received
Received 05 Apr, 2021
Review #1 received
Received 11 Mar, 2021
Reviewer #4 agreed
On 09 Mar, 2021
Reviewer #3 agreed
On 06 Mar, 2021
Reviewer #2 agreed
On 06 Mar, 2021
Review #2 received
Received 06 Mar, 2021
Reviewer #1 agreed
On 27 Feb, 2021
Reviewers invited
Invitations sent on 24 Feb, 2021
Editor assigned
On 30 Sep, 2020
Editor invited
On 29 Sep, 2020
Submission checks complete
On 10 Sep, 2020
First submitted
On 09 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Internal Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Despite the expectations regarding the effectiveness of chloroquine (CQ) and hydroxychloroquine (HCQ) for coronavirus disease (COVID-19) management, concerns about their adverse events have remained.
Objectives: The objective of this systematic review was to evaluate the safety of CQ and HCQ from malarial and non-malarial randomized clinical trials (RCTs).
Methods: The primary outcomes were the frequencies of serious adverse events (SAEs), retinopathy, and cardiac complications. Search strategies were applied to MEDLINE, EMBASE, LILACS, CENTRAL, Scopus, and Trip databases. We used random-effects model to pool results across studies and Peto one-step odds ratio (OR) for event rates below 1 %. Both-armed zero-event studies were excluded from the meta-analyses. We used the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate the certainty of evidence.
Results: Ninety-two RCTs were included. We found no significant difference between CQ/HCQ and control (placebo or non-CQ/HCQ) in the frequency of SAEs (OR: 0.98, 95 % confidence interval [CI]: 0.71–1.36, 25 trials, 11,605 participants, moderate certainty of evidence). No clear relationship was observed between CQ/HCQ and retinopathy (OR: 1,63, 95 % CI: -0.4–6.57, 5 trials, 344 participants, very low certainty of evidence). There was a low certainty of evidence of the effect of CQ/HCQ versus control on cardiac complications (Relative risk: 1.48, 95 % CI: 1.1–1.98, 8 trials, 5,970 participants).
Conclusions: CQ and HCQ might be safe, with low frequency of SAEs on malarial and non-malarial conditions. No clear effect of their use on the incidence of retinopathy and cardiac complications was observed.
The protocol for this systematic review was registered with PROSPERO (registration number: CRD42020177818)
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
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