Introduction: Acute lung injury and acute respiratory distress syndrome are common complications in patients with coronavirus disease 2019 (COVID-19). Poor outcomes in patients with COVID-19 are associated with cytokine release syndrome. Binding of interleukin-8 (CXCL8/IL-8) to its chemokine receptors, CXCR1/2, may mediate this inflammatory process. The aim of this clinical trial was to determine if CXCR1/2 blockade with reparixin can improve clinical outcomes in hospitalized patients with severe COVID-19 pneumonia. The dose and safety of reparixin have been investigated in clinical trials of patients with metastatic breast cancer. Methods: This was a phase 2, open-label, multicenter, randomized study in hospitalized adult patients with severe COVID-19 pneumonia from May 5, 2020 until November 27, 2020. Patients were randomized 2:1 to receive 1200 mg reparixin orally three times daily or standard of care (SOC) for up to 21 days. The primary endpoint was defined as a composite of clinical events: use of supplemental oxygen, need for mechanical ventilation, intensive care unit admission, and/or use of rescue medication. Results: Fifty-five patients were enrolled between reparixin (n = 36) and SOC (n = 19). The rate of clinical events was statistically significantly lower in the reparixin group compared with the SOC group (16.7% [95% CI 6.4-32.8%] vs. 42.1% [95% CI 20.3-66.5%], P = 0.02). The sensitivity analysis based on the Cox regression model provided an adjusted hazard ratio of 0.33 with statistical significance lower than 0.05 (95% CI 0.11-0.99; P = 0.047). Reparixin treatment appeared to be well tolerated. Conclusion: In patients with severe COVID-19, reparixin led to an improvement in clinical outcomes when compared with the SOC. A larger phase 3 clinical study is needed to confirm these results.

A multicenter phase 2 randomized controlled study on the efficacy and safety of reparixin in the treatment of hospitalized patients with COVID-19 pneumonia / G. Landoni, L. Piemonti, A. D'Arminio Monforte, P. Grossi, A. Zangrillo, E. Bucci, M. Allegretti, G. Goisis, E.M. Gavioli, N. Patel, M. De Pizzol, G. Pasedis, F. Mantelli. - In: INFECTIOUS DISEASES AND THERAPY. - ISSN 2193-6382. - (2022 May 26). [Epub ahead of print] [10.1007/s40121-022-00644-6]

A multicenter phase 2 randomized controlled study on the efficacy and safety of reparixin in the treatment of hospitalized patients with COVID-19 pneumonia

Piemonti, Lorenzo;D'Arminio Monforte, Antonella;De Pizzol, Maria;
2022-05-26

Abstract

Introduction: Acute lung injury and acute respiratory distress syndrome are common complications in patients with coronavirus disease 2019 (COVID-19). Poor outcomes in patients with COVID-19 are associated with cytokine release syndrome. Binding of interleukin-8 (CXCL8/IL-8) to its chemokine receptors, CXCR1/2, may mediate this inflammatory process. The aim of this clinical trial was to determine if CXCR1/2 blockade with reparixin can improve clinical outcomes in hospitalized patients with severe COVID-19 pneumonia. The dose and safety of reparixin have been investigated in clinical trials of patients with metastatic breast cancer. Methods: This was a phase 2, open-label, multicenter, randomized study in hospitalized adult patients with severe COVID-19 pneumonia from May 5, 2020 until November 27, 2020. Patients were randomized 2:1 to receive 1200 mg reparixin orally three times daily or standard of care (SOC) for up to 21 days. The primary endpoint was defined as a composite of clinical events: use of supplemental oxygen, need for mechanical ventilation, intensive care unit admission, and/or use of rescue medication. Results: Fifty-five patients were enrolled between reparixin (n = 36) and SOC (n = 19). The rate of clinical events was statistically significantly lower in the reparixin group compared with the SOC group (16.7% [95% CI 6.4-32.8%] vs. 42.1% [95% CI 20.3-66.5%], P = 0.02). The sensitivity analysis based on the Cox regression model provided an adjusted hazard ratio of 0.33 with statistical significance lower than 0.05 (95% CI 0.11-0.99; P = 0.047). Reparixin treatment appeared to be well tolerated. Conclusion: In patients with severe COVID-19, reparixin led to an improvement in clinical outcomes when compared with the SOC. A larger phase 3 clinical study is needed to confirm these results.
COVID-19; CXCR1/2; IL-8; Reparixin; SARS-COV-2
Settore MED/17 - Malattie Infettive
26-mag-2022
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/929365
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