Multicenter point prevalence evaluation of the utilization and safety of drug therapies for COVID-19 at the onset of the pandemic timeline in the United States

  1. Nathaniel J Rhodes
  2. Atheer Dairem
  3. William J Moore
  4. Anooj Shah
  5. Michael J Postelnick
  6. Melissa E Badowski
  7. Sarah M Michienzi
  8. Jaime L Borkowski
  9. Radhika S Polisetty
  10. Karen Fong
  11. Emily S Spivak
  12. James R Beardsley
  13. Cory M Hale
  14. Andrea M Pallotta
  15. Pavithra Srinivas
  16. Lucas T Schulz

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Abstract

Key points

In a multicenter point-prevalence study, we found that the rate of supportive care was high; among those receiving COVID-19 drug therapies, adverse reactions occurred in 12% of patients.

Purpose

There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period.

Methods

We conducted a noninterventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19–targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs).

Results

A total of 352 patients treated for COVID-19 at 15 US hospitals From April 18 to May 8, 2020, were included in the study. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies used included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 antagonists (9%). Five patients (7.5%) were receiving combination therapy. The rate of use of COVID-19–directed drug therapy was higher in patients with vs patients without a history of asthma (14.9% vs 7%, P = 0.037) and in patients enrolled in clinical trials (26.9% vs 3.2%, P < 0.001). Among those receiving drug therapy, 8 patients (12%) experienced an ADR, and ADRs were recognized at a higher rate in patients enrolled in clinical trials (62.5% vs 22%; odds ratio, 5.9; P = 0.028).

Conclusion

While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy, including those enrolled in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 treatments.

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  1. Version published to 10.1093/ajhp/zxaa426
  2. ScreenIT

    SciScore for 10.1101/2020.06.03.20121558: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was reviewed by each participating organization’s individual Institutional Review Board and found to be exempt.
    Consent: A waiver of informed consent and HIPAA authorization was completed at each site.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Study data were collected and managed using REDCap electronic data capture tools hosted at Northwestern University.
    REDCap
    suggested: (REDCap, RRID:SCR_003445)

    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:
    Whereas the agents above have known limitations, other agents including IL-6 inhibitors (tocilizumab, sarilumab), IL-1 inhibitors (anakinra, canakinumab), and remdesivir are gaining increased attention. The IL-6 inhibitor, tocilizumab, appeared beneficial in critically ill patients with severe COVID-19 based upon improvements in oxygen requirements, fever resolution, lung imaging, and inflammatory markers.21 Preliminary data from randomized, placebo-controlled, trial of sarilumab showed clinical improvements in patients with critical COVID-19.22 However, these treatments are not without risks as agents targeting the cytokine response may increase the risk for secondary infections, gastrointestinal perforations, and hepatic toxicity.23 Comprehensive information regarding the safety of these as yet unproven agents is needed as their use becomes more common in patients with COVID-19. Remdesivir has garnered considerable interest as a treatment for COVID-19 since May 2020 when it was granted EUA status.13 A recent randomized placebo controlled trial by Wang et al. did not establish significant benefit of remdesivir and was terminated early.24 Serious adverse events occurred in 18% and 26% of patients receiving remdesivir and placebo, respectively. ACTT-1 was a randomized, placebo-controlled, study of 1,063 hospitalized patients with COVID-19.25 Preliminary results showed a shorter median time to recovery with remdesivir (11 vs 15 days). Serious adverse events occurred in 21% and ...

    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.

    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 checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.06.03.20121558v1 on medRxiv