Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study)

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• dc.contributor.author Welte, Tobias
• dc.contributor.author Álvarez Lerma, Francisco
• dc.contributor.author Torres, Antoni
• dc.date.accessioned 2018-11-21T08:31:55Z
• dc.date.available 2018-11-21T08:31:55Z
• dc.date.issued 2018
• dc.description.abstract PURPOSE: The CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG as add-on therapy for patients with severe community-acquired pneumonia (sCAP). METHODS: In this double-blind, phase II study (NCT01420744), 160 patients with sCAP requiring invasive mechanical ventilation were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all-cause and pneumonia-related mortality. Safety and tolerability were monitored. Exploratory post hoc analyses were performed in subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L). RESULTS: Overall, there was no statistically significant difference in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p = 0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p = 0.465). Time to discharge from intensive care unit and mean duration of hospitalization were comparable between groups. Adverse-event incidences were comparable. Post hoc subset analyses, which included the majority of patients (58-78%), showed significant reductions in all-cause mortality (trimodulin vs. placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline. CONCLUSIONS: No significant differences were found in VFDs and mortality between trimodulin and placebo groups. Post hoc analyses supported improved outcome regarding mortality with trimodulin in subsets of patients with elevated CRP, reduced IgM, or both. These findings warrant further investigation.
• dc.format.mimetype application/pdf
• dc.identifier.citation Welte T, Dellinger RP, Ebelt H, Ferrer M, Opal SM, Singer M. et al. Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study). Intensive Care Med. 2018 Apr;44(4):438-448. DOI: 10.1007/s00134-018-5143-7
• dc.identifier.doi http://dx.doi.org/10.1007/s00134-018-5143-7
• dc.identifier.issn 0342-4642
• dc.identifier.uri http://hdl.handle.net/10230/35805
• dc.language.iso eng
• dc.publisher Springer
• dc.relation.ispartof Intensive Care Medicine. 2018 Apr;44(4):438-48
• dc.rights Copyright © The Author(s) 2018. Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.keyword Add-on therapy
• dc.subject.keyword Immunoglobulin M
• dc.subject.keyword Polyclonal antibody
• dc.subject.keyword Severe community-acquired pneumonia
• dc.subject.keyword Trimodulin
• dc.title Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study)
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion