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.