Lead Investigator: Nicholas White, Mahidol University
Title of Proposal Research: A Multiple-Dose Study to Assess the Effects of Azithromycin plus Chloroquine on Electrocardiograms in Healthy Subjects – COVID-19
Vivli Data Request: 6006
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Chloroquine, hydroxychloroquine and azithromycin have been widely recommended and used in COVID-19. There has been more interest in these drugs than any other interventions with strong statements about safety and toxicity which have not been evidence-based. In particular the effect of chloroquine or hydroxychloroquine on the electrocardiogram (ECG) (notably QT prolongation) has been a focus of concern. This is now the main reason for stopping studies and stopping medications in individuals. We wish to conduct an individual patient meta-analysis of the relationship between plasma concentrations of the parent drug and metabolite and the ECG changes to provide a sound evidence base and guidance for currently used COVID-19 drug regimens. We will combine individual data from healthy volunteers, malaria patients chloroquine self-poisoning. Until we gather all the data we cannot give precise numbers but the approximate total of subjects studied will be 200. All except the requested Pfizer data have been published in peer review open access journals.
Statistical Analysis Plan:
We will conduct a pharmacometric analysis of the relationship between plasma concentrations of chloroquine and desethylchloroquine, azithromycin, and the two drugs together the electrocardiograph intervals (PR, QRS, JT). This will be a standard mixed-effects pharmacometric modelling approach.
Requested Studies:
This is a healthy volunteer crossover study which assessed the electrocardiographic effects of chloroquine, azithromycin and the two combined
Sponsor: Pfizer
Sponsor ID: A0661139
Public Disclosure:
Chotsiri, P., Tarning, J., Hoglund, R.M., Watson, J. and White, N.J. (2022), Pharmacometric and electrocardiographic evaluation of chloroquine and azithromycin in healthy volunteers. Clin Pharmacol Ther. doi:10.1002/cpt.2665