Efficacy and safety of trimodulin in patients with severe COVID-19: results from a randomised, placebo-controlled, double-blind, multicentre, phase II trial (ESsCOVID).
COVID-19
Early systemic inflammation
Immunoglobulin
Immunomodulation
Trimodulin
Journal
European journal of medical research
ISSN: 2047-783X
Titre abrégé: Eur J Med Res
Pays: England
ID NLM: 9517857
Informations de publication
Date de publication:
13 Aug 2024
13 Aug 2024
Historique:
received:
15
04
2024
accepted:
01
08
2024
medline:
14
8
2024
pubmed:
14
8
2024
entrez:
13
8
2024
Statut:
epublish
Résumé
Trimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death. Adults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6-29) and 28-day all-cause mortality (Days 1-29). One-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable. A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (< 130 × 10 Although there was no difference in the primary outcome in the overall population, observations in a subgroup of patients with early systemic inflammation suggest that trimodulin may have potential in this setting that warrants further investigation. ESSCOVID WAS REGISTERED PROSPECTIVELY AT CLINICALTRIALS.GOV ON OCTOBER 6, 2020.: NCT04576728.
Sections du résumé
BACKGROUND
BACKGROUND
Trimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death.
METHODS
METHODS
Adults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6-29) and 28-day all-cause mortality (Days 1-29).
RESULTS
RESULTS
One-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable. A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (< 130 × 10
CONCLUSION
CONCLUSIONS
Although there was no difference in the primary outcome in the overall population, observations in a subgroup of patients with early systemic inflammation suggest that trimodulin may have potential in this setting that warrants further investigation. ESSCOVID WAS REGISTERED PROSPECTIVELY AT CLINICALTRIALS.GOV ON OCTOBER 6, 2020.: NCT04576728.
Identifiants
pubmed: 39138518
doi: 10.1186/s40001-024-02008-x
pii: 10.1186/s40001-024-02008-x
doi:
Substances chimiques
trimodulin
0
Drug Combinations
0
Immunoglobulin A
0
Immunoglobulin G
0
Immunoglobulin M
0
Banques de données
ClinicalTrials.gov
['NCT04576728']
Types de publication
Journal Article
Randomized Controlled Trial
Clinical Trial, Phase II
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
418Informations de copyright
© 2024. The Author(s).
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