tetano
Editor, Senior Moderator
Infect Dis Ther
. 2023 Oct 5.
doi: 10.1007/s40121-023-00871-5. Online ahead of print. Efficacy and Safety of Reparixin in Patients with Severe COVID-19 Pneumonia: A Phase 3, Randomized, Double-Blind Placebo-Controlled Study
Lorenzo Piemonti[SUP] 1 [/SUP], Giovanni Landoni[SUP] 2 3 [/SUP], Antonio Voza[SUP] 4 5 [/SUP], Massimo Puoti[SUP] 6 [/SUP], Ivan Gentile[SUP] 7 [/SUP], Nicola Coppola[SUP] 8 [/SUP], Stefano Nava[SUP] 9 10 [/SUP], Alessia Mattei[SUP] 11 [/SUP], Franco Marinangeli[SUP] 12 [/SUP], Giulia Marchetti[SUP] 13 [/SUP], Paolo Bonfanti[SUP] 14 15 [/SUP], Claudio Maria Mastroianni[SUP] 16 [/SUP], Matteo Bassetti[SUP] 17 18 [/SUP], Ernesto Crisafulli[SUP] 19 [/SUP], Paolo Antonio Grossi[SUP] 20 [/SUP], Alberto Zangrillo[SUP] 2 3 [/SUP], Antonio Desai[SUP] 4 5 [/SUP], Marco Merli[SUP] 6 [/SUP], Maria Foggia[SUP] 7 [/SUP], Marco Carpano[SUP] 9 10 [/SUP], Lorenzo Schiavoni[SUP] 11 [/SUP], Antonella D'Arminio Monforte[SUP] 13 [/SUP], Luca Bisi[SUP] 14 [/SUP], Gianluca Russo[SUP] 16 [/SUP], Fabiana Busti[SUP] 19 [/SUP], Cristina Rovelli[SUP] 20 [/SUP], Elisabetta Perrotta[SUP] 21 [/SUP], Giovanni Goisis[SUP] 21 [/SUP], Elizabeth M Gavioli[SUP] 21 [/SUP], Sophie Toya[SUP] 21 [/SUP], Maria De Pizzol[SUP] 21 [/SUP], Flavio Mantelli[SUP] 21 [/SUP], Marcello Allegretti[SUP] 21 [/SUP], Enrico Maria Minnella[SUP] 22 [/SUP]
Affiliations
Introduction: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia.
Methods: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28.
Results: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment.
Conclusions: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated.
Trial registration: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51.
Keywords: COVID-19; Interleukin-8 (IL-8); Reparixin; SARS-CoV-2.
. 2023 Oct 5.
doi: 10.1007/s40121-023-00871-5. Online ahead of print. Efficacy and Safety of Reparixin in Patients with Severe COVID-19 Pneumonia: A Phase 3, Randomized, Double-Blind Placebo-Controlled Study
Lorenzo Piemonti[SUP] 1 [/SUP], Giovanni Landoni[SUP] 2 3 [/SUP], Antonio Voza[SUP] 4 5 [/SUP], Massimo Puoti[SUP] 6 [/SUP], Ivan Gentile[SUP] 7 [/SUP], Nicola Coppola[SUP] 8 [/SUP], Stefano Nava[SUP] 9 10 [/SUP], Alessia Mattei[SUP] 11 [/SUP], Franco Marinangeli[SUP] 12 [/SUP], Giulia Marchetti[SUP] 13 [/SUP], Paolo Bonfanti[SUP] 14 15 [/SUP], Claudio Maria Mastroianni[SUP] 16 [/SUP], Matteo Bassetti[SUP] 17 18 [/SUP], Ernesto Crisafulli[SUP] 19 [/SUP], Paolo Antonio Grossi[SUP] 20 [/SUP], Alberto Zangrillo[SUP] 2 3 [/SUP], Antonio Desai[SUP] 4 5 [/SUP], Marco Merli[SUP] 6 [/SUP], Maria Foggia[SUP] 7 [/SUP], Marco Carpano[SUP] 9 10 [/SUP], Lorenzo Schiavoni[SUP] 11 [/SUP], Antonella D'Arminio Monforte[SUP] 13 [/SUP], Luca Bisi[SUP] 14 [/SUP], Gianluca Russo[SUP] 16 [/SUP], Fabiana Busti[SUP] 19 [/SUP], Cristina Rovelli[SUP] 20 [/SUP], Elisabetta Perrotta[SUP] 21 [/SUP], Giovanni Goisis[SUP] 21 [/SUP], Elizabeth M Gavioli[SUP] 21 [/SUP], Sophie Toya[SUP] 21 [/SUP], Maria De Pizzol[SUP] 21 [/SUP], Flavio Mantelli[SUP] 21 [/SUP], Marcello Allegretti[SUP] 21 [/SUP], Enrico Maria Minnella[SUP] 22 [/SUP]
Affiliations
- PMID: 37798468
- DOI: 10.1007/s40121-023-00871-5
Introduction: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia.
Methods: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28.
Results: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment.
Conclusions: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated.
Trial registration: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51.
Keywords: COVID-19; Interleukin-8 (IL-8); Reparixin; SARS-CoV-2.