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Adjunctive Recombinant Human Plasma Gelsolin for Severe Coronavirus Disease 2019 Pneumonia
BACKGROUND: Excessive inflammation contributes to the morbidity and mortality of severe coronavirus disease 2019 (COVID-19) pneumonia. Recombinant human plasma gelsolin (rhu-pGSN) improves disease outcomes in diverse experimental models of infectious and noninfectious inflammation. METHODS: In a bli...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345409/ https://www.ncbi.nlm.nih.gov/pubmed/35928505 http://dx.doi.org/10.1093/ofid/ofac357 |
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author | DiNubile, Mark J Parra, Sandra Salomó, Antoni Castro Levinson, Susan L |
author_facet | DiNubile, Mark J Parra, Sandra Salomó, Antoni Castro Levinson, Susan L |
author_sort | DiNubile, Mark J |
collection | PubMed |
description | BACKGROUND: Excessive inflammation contributes to the morbidity and mortality of severe coronavirus disease 2019 (COVID-19) pneumonia. Recombinant human plasma gelsolin (rhu-pGSN) improves disease outcomes in diverse experimental models of infectious and noninfectious inflammation. METHODS: In a blinded, randomized study, 61 subjects with documented COVID-19 pneumonia having a World Health Organization (WHO) Severity Score of 4 to 6 and evidence of a hyperinflammatory state were treated with standard care and either adjunctive rhu-pGSN 12 mg/kg or an equal volume of saline placebo given intravenously at entry, 12 hours, and 36 hours. The prespecified coprimary outcomes were survival without major respiratory, hemodynamic, or renal support on Day 14 and the incidence of serious adverse events (SAEs) during the 90-day study period. RESULTS: All subjects receiving ≥1 dose of study drug were analyzed. Fifty-four of 61 subjects (88.5%) were WHO severity level 4 at entry. The proportions of subjects alive without support on Day 14 were 25 of 30 rhu-pGSN recipients (83.3%) and 27 of 31 placebo recipients (87.1%). Over the duration of the study, WHO Severity Scores improved similarly in both treatment groups. No statistically significant differences were observed between treatment groups at any time point examined. Two subjects died in each group. Numerically fewer subjects in the rhu-pGSN group had SAEs (5 subjects; 16.7%) or ≥ Grade 3 adverse events (5 subjects; 16.7%) than in the placebo group (8 subjects [25.8%] and 9 subjects [29.0%], respectively), mostly involving the lungs. Three rhu-pGSN recipients (10.0%) were intubated compared to 6 placebo recipients (19.4%). CONCLUSIONS: Overall, subjects in this study did well irrespective of treatment arm. When added to dexamethasone and remdesivir, no definitive benefit was demonstrated for rhu-pGSN relative to placebo. Safety signals were not identified after the administration of 3 doses of 12 mg/kg rhu-pGSN over 36 hours. The frequencies of SAEs and intubation were numerically fewer in the rhu-pGSN group compared with placebo. |
format | Online Article Text |
id | pubmed-9345409 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-93454092022-08-03 Adjunctive Recombinant Human Plasma Gelsolin for Severe Coronavirus Disease 2019 Pneumonia DiNubile, Mark J Parra, Sandra Salomó, Antoni Castro Levinson, Susan L Open Forum Infect Dis Major Article BACKGROUND: Excessive inflammation contributes to the morbidity and mortality of severe coronavirus disease 2019 (COVID-19) pneumonia. Recombinant human plasma gelsolin (rhu-pGSN) improves disease outcomes in diverse experimental models of infectious and noninfectious inflammation. METHODS: In a blinded, randomized study, 61 subjects with documented COVID-19 pneumonia having a World Health Organization (WHO) Severity Score of 4 to 6 and evidence of a hyperinflammatory state were treated with standard care and either adjunctive rhu-pGSN 12 mg/kg or an equal volume of saline placebo given intravenously at entry, 12 hours, and 36 hours. The prespecified coprimary outcomes were survival without major respiratory, hemodynamic, or renal support on Day 14 and the incidence of serious adverse events (SAEs) during the 90-day study period. RESULTS: All subjects receiving ≥1 dose of study drug were analyzed. Fifty-four of 61 subjects (88.5%) were WHO severity level 4 at entry. The proportions of subjects alive without support on Day 14 were 25 of 30 rhu-pGSN recipients (83.3%) and 27 of 31 placebo recipients (87.1%). Over the duration of the study, WHO Severity Scores improved similarly in both treatment groups. No statistically significant differences were observed between treatment groups at any time point examined. Two subjects died in each group. Numerically fewer subjects in the rhu-pGSN group had SAEs (5 subjects; 16.7%) or ≥ Grade 3 adverse events (5 subjects; 16.7%) than in the placebo group (8 subjects [25.8%] and 9 subjects [29.0%], respectively), mostly involving the lungs. Three rhu-pGSN recipients (10.0%) were intubated compared to 6 placebo recipients (19.4%). CONCLUSIONS: Overall, subjects in this study did well irrespective of treatment arm. When added to dexamethasone and remdesivir, no definitive benefit was demonstrated for rhu-pGSN relative to placebo. Safety signals were not identified after the administration of 3 doses of 12 mg/kg rhu-pGSN over 36 hours. The frequencies of SAEs and intubation were numerically fewer in the rhu-pGSN group compared with placebo. Oxford University Press 2022-07-25 /pmc/articles/PMC9345409/ /pubmed/35928505 http://dx.doi.org/10.1093/ofid/ofac357 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Major Article DiNubile, Mark J Parra, Sandra Salomó, Antoni Castro Levinson, Susan L Adjunctive Recombinant Human Plasma Gelsolin for Severe Coronavirus Disease 2019 Pneumonia |
title | Adjunctive Recombinant Human Plasma Gelsolin for Severe Coronavirus Disease 2019 Pneumonia |
title_full | Adjunctive Recombinant Human Plasma Gelsolin for Severe Coronavirus Disease 2019 Pneumonia |
title_fullStr | Adjunctive Recombinant Human Plasma Gelsolin for Severe Coronavirus Disease 2019 Pneumonia |
title_full_unstemmed | Adjunctive Recombinant Human Plasma Gelsolin for Severe Coronavirus Disease 2019 Pneumonia |
title_short | Adjunctive Recombinant Human Plasma Gelsolin for Severe Coronavirus Disease 2019 Pneumonia |
title_sort | adjunctive recombinant human plasma gelsolin for severe coronavirus disease 2019 pneumonia |
topic | Major Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345409/ https://www.ncbi.nlm.nih.gov/pubmed/35928505 http://dx.doi.org/10.1093/ofid/ofac357 |
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