A multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate coronavirus disease 2019 (COVID-19)
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study.
Methods
Subjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ (400 mg twice for 1 d or HCQ 200 mg twice daily for 6 days) was administered. Both the study and control group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020.
Results
There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1, 9 days) and 10 days (95% CI; 2, 12 days) for the HCQ and SOC groups, respectively ( p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus ( p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 ( p = 0.70).
Conclusions
Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.
Article activity feed
-
SciScore for 10.1101/2020.07.08.20148841: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethical statement: The study protocol was approved by the Institutional Review Board of Taoyuan General Hospital (IRB No. TYGH109014). Randomization Study design: Eligible subjects were randomly assigned by an interactive web response system in a 2:1 ratio to receive either HCQ plus standard of care (SOC) or SOC alone. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Statistical analysis: Data were entered into an electronic clinical trial information management system (CTIMeS; National Health Research Institutes, Taiwan) by study coordinators and summarized … SciScore for 10.1101/2020.07.08.20148841: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethical statement: The study protocol was approved by the Institutional Review Board of Taoyuan General Hospital (IRB No. TYGH109014). Randomization Study design: Eligible subjects were randomly assigned by an interactive web response system in a 2:1 ratio to receive either HCQ plus standard of care (SOC) or SOC alone. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Statistical analysis: Data were entered into an electronic clinical trial information management system (CTIMeS; National Health Research Institutes, Taiwan) by study coordinators and summarized with SAS® v. 9.2 (SAS Institute Inc., Cary, NC, USA) All treatment data will be summarized using descriptive statistics including continuous variables (number of non-missing observations, means, standard deviations (SD), medians, minima, and maxima), categorical variables (frequencies and percentages), and time to event variables (number of non-missing observations (N), medians, minima, and maxima). SAS®suggested: (SASqPCR, RRID:SCR_003056)SAS Institutesuggested: (Statistical Analysis System, RRID:SCR_008567)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:In contrast, there were limitations to the present study. Only patients presenting with mild to moderate disease symptoms were enrolled in order to determine the viral clearance efficacy of HCQ. Hence, there is relatively little data on the impact of severe disease in terms of intubation and mortality. At clinical trial launch, there were no indigenous and very few imported cases in Taiwan. Therefore, study enrollment was prematurely stopped. The low case numbers in the present study might account for the apparent lack of superior efficacy of HCQ. However, 81% of the HCQ group and 75% of the SOC group had confirmed viral clearance on hospital day 14. Moreover, according to Taiwan CDC regulations, subjects could not be off-quarantine until they presented with at least three consecutive negative rRT-PCR results. The outcome of this RCT may assist the Taiwan CDC in their decision to release quarantined patients when medical resources are in short supply. Another limitation of the study was that the mean patient age (SD) was 32.9 (10.7) y as opposed to 51.1 y (13.9) for Borba et al., 45.1 y for Gautret et al., 44.7 y (15.3) for Chen et al., and 46.1 y (14.7) for Tang et al. [15,27,31,32]. For this reason, the observed rates of cardiac and retinal toxicity were low in the present study. Electrocardiogram monitoring was performed frequently and close attention was paid to any changes in patient QTc interval, vision, and neurological symptoms. Lastly, readers might question about th...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04384380 Completed Efficacy and Tolerability of Hydroxychloroquine in Adult Pat… NCT04261517 Completed Efficacy and Safety of Hydroxychloroquine for Treatment of C… 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.
-
-
SciScore for 10.1101/2020.07.08.20148841: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement They provided signed informed consent. Randomization Abstract Objective In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study. Blinding not detected. Power Analysis not detected. Sex as a biological variable The following patients were excluded from the trial: (a) documented history of hypersensitivity to quinine derivatives; (b) retinal disease; (c) hearing loss; (d) severe neurological or mental illness; (e) pancreatitis; (f) lung disease; (g) liver disease (alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 3× the … SciScore for 10.1101/2020.07.08.20148841: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement They provided signed informed consent. Randomization Abstract Objective In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study. Blinding not detected. Power Analysis not detected. Sex as a biological variable The following patients were excluded from the trial: (a) documented history of hypersensitivity to quinine derivatives; (b) retinal disease; (c) hearing loss; (d) severe neurological or mental illness; (e) pancreatitis; (f) lung disease; (g) liver disease (alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 3× the normal upper limit); (h) kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2 according to MDRD or CKD-EPI); (i) hematological disease; (j) cardiac conduction abnormalities at electrocardiographic (ECG) screening with long QT syndrome or QTcF interval > 450 msec for males and > 470 msec for females according to Fridericia’s correction at screening; (k) known HIV infection; (l) active hepatitis B or C without concurrent treatment (positive for hepatitis B [HBsAg and HBeAg] or hepatitis C ribonucleic acid [RNA] titer > 800,000 IU/mL); (m) G6PD; (n) psychiatric disorders and alcohol/substance dependence/abuse that may jeopardize patient safety; and (o) pregnant or breast-feeding women. Table 2: Resources
Software and Algorithms Sentences Resources Statistical analysis Data were entered into an electronic clinical trial information management system (CTIMeS; National Health Research Institutes, Taiwan) by study coordinators and summarized with SAS® v. 9.2 (SAS Institute Inc., Cary, NC, USA) All treatment data will be summarized using descriptive statistics including continuous variables (number of non-missing observations, means, standard deviations (SD), medians, minima, and maxima), categorical variables (frequencies and percentages), and time to event variables (number of non-missing observations (N), medians, minima, and maxima). SAS®suggested: (SASqPCR, SCR_003056)<div style="margin-bottom:8px"> <div><b>SAS Institute</b></div> <div>suggested: (Statistical Analysis System, <a href="https://scicrunch.org/resources/Any/search?q=SCR_008567">SCR_008567</a>)</div> </div> </td></tr></table>Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.
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).
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.
-
