A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia

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 receptor...

Full description

Saved in:
Bibliographic Details
Published in:Infectious diseases and therapy 2022-08, Vol.11 (4), p.1559-1574
Main Authors: Landoni, Giovanni, Piemonti, Lorenzo, Monforte, Antonella d’Arminio, Grossi, Paolo, Zangrillo, Alberto, Bucci, Enrico, Allegretti, Marcello, Goisis, Giovanni, Gavioli, Elizabeth M., Patel, Neal, De Pizzol, Maria, Pasedis, Georgea, Mantelli, Flavio
Format: Article
Language:English
Subjects:
Acute respiratory distress syndrome
Analysis
Bacterial pneumonia
Care and treatment
Clinical outcomes
Clinical trials
Coronaviruses
COVID-19
Hospital patients
Hospitalization
Infectious Diseases
Interleukins
Internal Medicine
Medical research
Medicine
Medicine & Public Health
Medicine, Experimental
Metastasis
NCT
NCT04794803
Original Research
Pneumonia
Product development
Sensitivity analysis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Trial Registration EudraCT identifier, 2020-001645-40; registered May 6, 2020 (retrospectively registered), and clinicaltrials.gov (NCT04794803) on March 8, 2021.
ISSN:2193-8229
2193-6382
DOI:10.1007/s40121-022-00644-6