Repurposing of NKA inhibitors (‘cardiac glycosides’): a critical analysis

Figures

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  Fig. 1. Flowchart of methods employed in analysing identified clinical trials for repurposing. The program in question is defined in ‘Program for analysis’ section Source codes: https://github.com/T-Specht/h1ra-repurpose/ and GitHub - T-Specht/clinical-trials-explorer

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  Fig. 2. Flowchart of the process of filtering studies regarding repurposing in absolute numbers. Trials marked for repurposing used NKA inhibitors for foreign indications. ‘Unknown publication status’ was used when a trial could not be matched to a publication with certainty. DIF, digoxin immune fab (an antidote for digoxin, not an NKA inhibitor, irrelevant). CT results pertain to results uploaded to ClinicalTrials.gov but not yet published in a paper

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  Fig. 3. Diagram showing the number of studies related to each drug color coded by the role the drug had in the study in absolute numbers. The drug role was derived from the use of the drug in the study and was not listed as such in ClinicalTrials.gov. Unclear: the role of the drug could not be determined from the study page or possible existing publications. Standard of care: drug was used as a standard of care and was not of interest to the study. Second-line therapy: drug was used as second-line therapy or as a rescue drug and was not a focus of the study. Safety analysis: the safety of the drug was analysed. The drug’s use itself was not focus of the study. Not of interest: NKA inhibitor was mentioned in the abstract, as either an exclusion criterion or as a baseline medication in the patients. They had no role in the study. None: there was no NKA inhibitor in use in the study. Main: NKA inhibitor was the main focus of the study. Comparator: drug was used as an active comparator for a different therapy and was not the main focus of the study. Combination: drug was used in combination with a different drug or therapy

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  Fig. 4. Diagram illustrating the publication status of studies in relation to the status the study was given by ClinicalTrials.gov in absolute numbers. This dataset was last revised on 28 November 2024. It is possible that in the meantime, status and publication status of some of these studies has changed. Active not recruiting: the study is ongoing, and participants are receiving an intervention or being examined, but potential participants are not currently being recruited or enrolled. Completed: the study has ended normally, and participants are no longer being examined or treated (that is, the last participant’s last visit has occurred). No longer available: information on this study is no longer available. Trial has been terminated or withdrawn. Not yet recruiting: the study has not started recruiting participants. Recruiting: the study is currently recruiting participants. Suspended: the study has stopped early but may start again. Terminated: the study has stopped early and will not start again. Participants are no longer being examined or treated. Withdrawn: the study stopped early, before enrolling its first participant. Unknown status is defined above…

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  Fig. 5. Diagram of the colour-coded publication status of the studies marked ‘repurposing’ in relation to the trial status (x axis) stated on the ClinicalTrials.gov website in percentage. The definitions can be found in caption of Fig. 4

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  Fig. 6. Chart illustrating the role the drug had in the study marked ‘repurposing’ (40 studies) by drug in absolute numbers. The NKA inhibitors examined were digoxin and digitoxin. Main: the drug was the main focus of the study. Combination: the drug was used in combination with other drugs

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  Fig. 7. Chart illustrating the different use cases for the ‘repurposed drugs’ in absolute numbers. Use cases were defined during analysis and derived largely from the study’s focus and outcome measures