Chloroquine for treatment of COVID-19 - a pig in a poke?
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Abstract
Objective
Chloroquine has been frequently administered for treatment of coronavirus disease 2019 but there are serious concerns about its efficacy and cardiac safety. Our objective was to investigate the pharmacokinetics and safety of chloroquine in hospitalized COVID-19 patients.
Design
A prospective observational study.
Setting
Dutch hospitals
Patients
Patients admitted to the hospital for treatment of COVID-19.
Interventions
Pharmacokinetic sampling
Measurements
The plasma concentrations of chloroquine and desethylchloroquine and QTc time.
Main Results
A total of 83 patients were included. The median (IQR) plasma concentration chloroquine during treatment was 1.05 μmol/L (0.63 - 1.55 μmol/L). None of the patients reached exposure exceeding the concentration to inhibit SARS-CoV-2 replication by 90% ( IC90 ) of 6.9 μM. Furthermore, ΔQTc >60 milliseconds occurred after initiation of chloroquine treatment in 34% patients and during treatment QTc ≥500 milliseconds was observed in 46% of patients.
Conclusions
Recommended dose chloroquine treatment results in plasma concentrations that are unlikely to inhibit viral replication. Furthermore, the incidence of QTc prolongation was high. The preclinical promise of chloroquine as antiviral treatment in patients with COVID-19 is overshadowed by its cardiac toxicity and lack of effective exposure. It is unlikely that a positive clinical effect will be found with chloroquine for treatment of COVID-19.
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SciScore for 10.1101/2020.07.06.20147470: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The institutional review boards of the Radboud University Medical Center and Leiden University Medical Center waived the need for formal ethics approval as all data were collected anonymously using minimally invasive measures. Randomization Plasma concentrations of chloroquine and its metabolite desethylchloroquine were measured in samples collected as a 4-point pharmacokinetic curve over an 8 hour interval or in randomly collected surplus samples from routine laboratory monitoring by means of a validated bioanalytical assay. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Re…
SciScore for 10.1101/2020.07.06.20147470: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The institutional review boards of the Radboud University Medical Center and Leiden University Medical Center waived the need for formal ethics approval as all data were collected anonymously using minimally invasive measures. Randomization Plasma concentrations of chloroquine and its metabolite desethylchloroquine were measured in samples collected as a 4-point pharmacokinetic curve over an 8 hour interval or in randomly collected surplus samples from routine laboratory monitoring by means of a validated bioanalytical assay. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
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: 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 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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