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Dear Editor,
We read the article by Landoni et al. with great interest and appreciate the author’s efforts to prove the efficacy and safety of reparixin in treating hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia [1]. However, we would like to highlight concerns regarding the rescue medication and intensive care unit (ICU) admission criteria in their randomized controlled trial (RCT).
First, the criteria for administering a “rescue medication” are unclear. The control group and the reparixin group might not have received rescue medication according to the same criteria. A predisposition toward treating patients assigned to the control group more attentively could have potentially increased the number of rescue medications. This could have led to a biased overestimation of the intervention effect on the primary endpoint.
Second, the admission criteria for the ICU may have varied among the four institutions that participated in this multicentric RCT. The decision to admit a patient into the ICU is taken considering several factors, including physician discretion, respiratory failure status, risk of serious illness, the availability of ICU beds for patients with COVID-19 during the COVID-19 pandemic, and institutional criteria for the ICU facility [2, 3]. Therefore, defining ICU admission as a composite clinical event might not be appropriate.
Third, as per Table 3, the number of composite clinical events, for all assessments except rescue medication, is not significant in the reparixin group compared with that in the control group.
We propose analyzing the primary endpoint after excluding the rescue medication and ICU admission, as per our first and second comments. We believe that this will help readers correctly interpret the findings of this study.
References
Landoni G, Piemonti L, Monforte AD, et al. A multicenter phase 2 randomized controlled study on the efficacy and safety of reparixin in the treatment of hospitalized patients with COVID-19 pneumonia. Infect Dis Ther. 2022;11:1559–74. https://doi.org/10.1007/s40121-022-00644-6.
Nates JL, Nunnally M, Kleinpell R, et al. ICU Admission, discharge, and triage guidelines: a framework to enhance clinical operations, development of institutional policies, and further research. Crit Care Med. 2016;44(8):1553–602. https://doi.org/10.1097/ccm.0000000000001856.
Oda J, Takashi M, Matsuyama S, et al. JAAM Nationwide Survey on the response to the first wave of COVID-19 in Japan Part II: how the medical institutions overcame the first wave and how to prepare in future? Acute Med Surg. 2020;7(1):592. https://doi.org/10.1002/ams2.592.
Acknowledgements
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No funding or sponsorship was received for this study or publication of this letter.
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The authors thank Enago (https://www.enago.jp) for the English language review.
Author Contributions
All authors contributed to the study conception and design. Material preparation and data collection were performed by Shun Ito, Masahiro Banno, and Yuji Okazaki. The first draft of the manuscript was written by Shun Ito, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Disclosures
Shun Ito, Masahiro Banno, and Yuji Okazaki have nothing to disclose.
Compliance with Ethics Guidelines
This letter is based on a previously conducted study and does not contain any study with human participants or animals performed by any of the authors.
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Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
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Ito, S., Banno, M. & Okazaki, Y. Letter to the Editor Regarding a Multicentric Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia. Infect Dis Ther 12, 299–300 (2023). https://doi.org/10.1007/s40121-022-00728-3
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DOI: https://doi.org/10.1007/s40121-022-00728-3