Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study
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Abstract
The outbreak of novel coronavirus disease 2019 (COVID-19) has become a pandemic. Drug repurposing may represent a rapid way to fill the urgent need for effective treatment. We evaluated the clinical utility of chloroquine and hydroxychloroquine in treating COVID-19.
Forty-eight patients with moderate COVID-19 were randomized to oral treatment with chloroquine (1000 mg QD on Day 1, then 500 mg QD for 9 days; n=18), hydroxychloroquine (200 mg BID for 10 days; n=18), or control treatment (n=12).
Adverse events were mild, except for one case of Grade 2 ALT elevation. Adverse events were more commonly observed in the chloroquine group (44.44%) and the hydroxychloroquine group (50.00%) than in the control group (16.67%). The chloroquine group achieved shorter time to clinical recovery (TTCR) than the control group (P=0.019). There was a trend toward reduced TTCR in the hydroxychloroquine group (P=0.049). The time to reach viral RNA negativity was significantly faster in the chloroquine group and the hydroxychloroquine group than in the control group (P=0.006 and P=0.010, respectively). The median numbers of days to reach RNA negativity in the chloroquine, hydroxychloroquine, and control groups was 2.5 (IQR: 2.0-3.8) days, 2.0 (IQR: 2.0-3.5) days, and 7.0 (IQR: 3.0-10.0) days, respectively. The chloroquine and hydroxychloroquine groups also showed trends toward improvement in the duration of hospitalization and findings on lung computerized tomography (CT). This study provides evidence that (hydroxy)chloroquine may be used effectively in treating moderate COVID-19 and supports larger trials.
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SciScore for 10.1101/2020.06.19.20136093: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The institution’s ethics committee approved this study.
Consent: Prior to screening, all enrolled patients signed their written informed consent.Randomization Study design and participation: From Feb 18 to Mar 30, 2020, we conducted a prospective, open-label, randomized and controlled study (Clinical Trial Registration Number: ChiCTR2000030054) at Ward E3-9, Optical Valley Campus of Tongji Hospital, Wuhan, Hubei Province, China. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Additionally exploratory biomarkers were measured: cytokines (IL-1β, IL-2R, IL-6, Il-8, IL-10, and … SciScore for 10.1101/2020.06.19.20136093: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The institution’s ethics committee approved this study.
Consent: Prior to screening, all enrolled patients signed their written informed consent.Randomization Study design and participation: From Feb 18 to Mar 30, 2020, we conducted a prospective, open-label, randomized and controlled study (Clinical Trial Registration Number: ChiCTR2000030054) at Ward E3-9, Optical Valley Campus of Tongji Hospital, Wuhan, Hubei Province, China. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Additionally exploratory biomarkers were measured: cytokines (IL-1β, IL-2R, IL-6, Il-8, IL-10, and TNFα) and SAR-CoV-2-specific IgG/IgM antibody. IL-2Rsuggested: NoneIL-6suggested: NoneIl-8suggested: NoneIL-10suggested: NoneTNFαsuggested: NoneSAR-CoV-2-specific IgG/IgMsuggested: NoneSoftware and Algorithms Sentences Resources SPSS v17.0 software was used for statistical analysis. SPSSsuggested: (SPSS, RRID:SCR_002865)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:There were a couple of limitations in the study. First, due to the unexpected onset of this epidemic and the availability of active drugs only, we were not able to conduct a placebo-controlled, double-blinded study, which would have been more objective and largely excluded the possible impact of open-label use on a given physician’s assessment. Second, because the Chinese government implemented a robust intervention approach that effectively controlled the epidemic, the study was terminated before full enrollment (n=40 each for the chloroquine and hydroxychloroquine groups, n=20 for the control group). Thus, while we demonstrated positive results, the study per se was underpowered. We used a one-month study period and a sample size of 30 (n=18 for (hydroxy)chloroquine vs. n=12 for control) to conduct a post-hoc power analysis. With the alpha level (single-sided) set at 0.025, we would only expect 13.7% (chloroquine vs. control) or 9.2% (hydroxychloroquine vs. control) power, respectively, for detection of a real difference in the median numbers of TTCR days (5.5 days, 6.0 days, and 7.5 days) for chloroquine, hydroxychloroquine and control treatment, respectively. In this study, the dosage regimen for chloroquine phosphate administration was based on the desire to maximize efficacy while minimizing safety concerns. According to the prescription label of chloroquine phosphate in China, the drug is licensed for the treatment of malaria, extraintestinal amebiasis, and rheumatoid ...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.06.19.20136093: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement The institution’s ethics committee approved this study. Randomization Forty-eight patients with moderate COVID-19 were randomized to oral treatment with chloroquine (1000 mg QD on Day 1, then 500 mg QD for 9 days; n=18), hydroxychloroquine (200 mg BID for 10 days; n=18), or control treatment (n=12). Blinding not detected. Power Analysis We used a one-month study period and a sample size of 30 (n=18 for (hydroxy)chloroquine vs. n=12 for control) to conduct a post-hoc power analysis. Sex as a biological variable The chloroquine arm had an average age of 45.22 ± 13.66 years, including 7 males (38.89%). Table 2: Resources
Antibodies Sentences Resources Addition… SciScore for 10.1101/2020.06.19.20136093: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement The institution’s ethics committee approved this study. Randomization Forty-eight patients with moderate COVID-19 were randomized to oral treatment with chloroquine (1000 mg QD on Day 1, then 500 mg QD for 9 days; n=18), hydroxychloroquine (200 mg BID for 10 days; n=18), or control treatment (n=12). Blinding not detected. Power Analysis We used a one-month study period and a sample size of 30 (n=18 for (hydroxy)chloroquine vs. n=12 for control) to conduct a post-hoc power analysis. Sex as a biological variable The chloroquine arm had an average age of 45.22 ± 13.66 years, including 7 males (38.89%). Table 2: Resources
Antibodies Sentences Resources Additionally exploratory biomarkers were measured: cytokines (IL-1β, IL-2R, IL-6, Il-8, IL-10, and TNFα) and SAR-CoV-2-specific IgG/IgM antibody. IL-2Rsuggested: None<div style="margin-bottom:8px"> <div><b>IL-6</b></div> <div>suggested: None</div> </div> <div style="margin-bottom:8px"> <div><b>Il-8</b></div> <div>suggested: None</div> </div> <div style="margin-bottom:8px"> <div><b>IL-10</b></div> <div>suggested: None</div> </div> <div style="margin-bottom:8px"> <div><b>TNFα</b></div> <div>suggested: None</div> </div> <div style="margin-bottom:8px"> <div><b>SAR-CoV-2-specific IgG/IgM</b></div> <div>suggested: None</div> </div> </td></tr><tr><td style="min-width:100px;text-align:center; padding-top:4px;" colspan="2"><b>Software and Algorithms</b></td></tr><tr><td style="min-width:100px;text=align:center"><i>Sentences</i></td><td style="min-width:100px;text-align:center"><i>Resources</i></td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">SPSS v17.0 software was used for statistical analysis.</td><td style="min-width:100px;border-bottom:1px solid lightgray"> <div style="margin-bottom:8px"> <div><b>SPSS</b></div> <div>suggested: (SPSS, <a href="https://scicrunch.org/resources/Any/search?q=SCR_002865">SCR_002865</a>)</div> </div> </td></tr></table>Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
- There were a couple of limitations in the study.
- First, due to the unexpected onset of this epidemic and the availability of active drugs only, we were not able to conduct a placebo-controlled, double-blinded study, which would have been more objective and largely excluded the possible impact of open-label use on a given physician's assessment.
- Second, because the Chinese government implemented a robust intervention approach that effectively controlled the epidemic, the study was terminated before full enrollment (n=40 each for the chloroquine and hydroxychloroquine groups, n=20 for the control group).
- Thus, while we demonstrated positive results, the study per se was underpowered.
- We used a one-month study period and a sample size of 30 (n=18 for (hydroxy)chloroquine vs.
Results from OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.
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