| Title: |
Sarilumab plus standard of care vs standard of care for the treatment of severe COVID-19: a phase 3, randomized, open-labeled, multi-center study (ESCAPE study) |
| Authors: |
Mastrorosa, I.; Gagliardini, R.; Mondi, A.; Lorenzini, P.; Cerva, C.; Vergori, A.; Pinnetti, C.; Cicalini, S.; Mazzotta, V.; Camici, M.; Mosti, S.; Maffongelli, G.; Beccacece, A.; Milozzi, E.; Fusto, M.; Plazzi, M. M.; Ottou, S.; Girardi, E.; Nicastri, E.; Palmieri, F.; Vaia, F.; Antinori, A.; Segala, F. V.; Taddei, E.; Marcantonio, N.; Murri, R.; Lamonica, S.; Fantoni, M.; Cauda, R.; Cingolani, A.; Bai, F.; Bini, T.; D(')Arminio Monforte, A.; Iannetta, M.; Andreoni, M.; Sarmati, L.; Lichtner, M.; Agrati, C.; Barreca, F.; Bertuccio, M. P.; Boumis, E.; D(')Urso, A.; De Masi, M.; De Zottis, F.; Del Borgo, C.; Di Gennaro, F.; Emiliozzi, A.; Fondaco, L.; Giovannenze, F.; Grilli, E.; Iodice, D.; Masone, E.; Massa, B.; Mencarini, P.; Negri, M.; Oliva, G. P.; Onnelli, G.; Pace, P. G.; Paulicelli, J.; Sorace, C.; Vitale, P. |
| Contributors: |
Mastrorosa, I; Gagliardini, R; Mondi, A; Lorenzini, P; Cerva, C; Vergori, A; Pinnetti, C; Cicalini, S; Mazzotta, V; Camici, M; Mosti, S; Maffongelli, G; Beccacece, A; Milozzi, E; Fusto, M; Plazzi, Mm; Ottou, S; Girardi, E; Nicastri, E; Palmieri, F; Vaia, F; Antinori, A; Segala, Fv; Taddei, E; Marcantonio, N; Murri, R; Lamonica, S; Fantoni, M; Cauda, R; Cingolani, A; Bai, F; Bini, T; D(')Arminio Monforte, A; Iannetta, M; Andreoni, M; Sarmati, L; Lichtner, M; Agrati, C; Barreca, F; Bertuccio, Mp; Boumis, E; D(')Urso, A; De Masi, M; De Zottis, F; Del Borgo, C; Di Gennaro, F; Emiliozzi, A; Fondaco, L; Giovannenze, F; Grilli, E; Iodice, D; Masone, E; Massa, B; Mencarini, P; Negri, M; Oliva, Gp; Onnelli, G; Pace, Pg; Paulicelli, J; Sorace, C; Vitale, P |
| Publisher Information: |
ELSEVIER |
| Publication Year: |
2023 |
| Collection: |
Universitá degli Studi di Roma "Tor Vergata": ART - Archivio Istituzionale della Ricerca |
| Subject Terms: |
Interleukin-6 receptor inhibitors; Randomized clinical trial; SARS-CoV-2 infection; Sarilumab; Severe COVID-19 pneumonia; Settore MED/17 |
| Description: |
Background Among interleukin-6 inhibitors suggested for use in COVID-19, there are few robust evidences for the efficacy of sarilumab. Herein, we evaluated the efficacy and safety of sarilumab in severe COVID-19.Methods In this phase 3, open-labeled, randomized clinical trial, conducted at 5 Italian hospitals, adults with severe COVID-19 pneumonia (excluding mechanically ventilated) were randomized 2:1 to receive intravenous sarilumab (400 mg, repeatable after 12 h) plus standard of care (SOC) (arm A) or to continue SOC (arm B). Randomization was web-based. As post-hoc analyses, the participants were stratified according to baseline inflammatory parameters. The primary endpoint was analysed on the modified Intention-To-Treat population, including all the randomized patients who received any study treatment (sarilumab or SOC). It was time to clinical improvement of 2 points on a 7-points ordinal scale, from baseline to day 30. We used Kaplan Meier method and log-rank test to compare the primary outcome between two arms, and Cox regression stratified by clinical center and adjusted for severity of illness, to estimate the hazard ratio (HR). The trial was registered with EudraCT (2020-001390-76).Findings Between May 2020 and May 2021, 191 patients were assessed for eligibility, of whom, excluding nine dropouts, 176 were assigned to arm A (121) and B (55). At day 30, no significant differences in the primary endpoint were found (88% [95% CI 81-94] in arm A vs 85% [74-93], HR 1.07 [0.8-1.5] in arm B; log-rank p = 0.50). After stratifying for inflammatory parameters, arm A showed higher probability of improvement than B without statistical significance in the strata with C reactive protein (CRP) < 7 mg/dL (88% [77-96] vs 79% [63-91], HR 1.55 [0.9-2.6]; log-rank p = 0.049) and in the strata with lymphocytes |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/36936403; info:eu-repo/semantics/altIdentifier/wos/WOS:000995007400001; volume:57; firstpage:1; lastpage:11; numberofpages:11; journal:ECLINICALMEDICINE; https://hdl.handle.net/2108/341823 |
| DOI: |
10.1016/j.eclinm.2023.101895 |
| Availability: |
https://hdl.handle.net/2108/341823; https://doi.org/10.1016/j.eclinm.2023.101895 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.97BB903F |
| Database: |
BASE |