Ontology highlight
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.Trial registration
NCT01420744.
SUBMITTER: Welte T
PROVIDER: S-EPMC5924663 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
Welte Tobias T Dellinger R Phillip RP Ebelt Henning H Ferrer Miguel M Opal Steven M SM Singer Mervyn M Vincent Jean-Louis JL Werdan Karl K Martin-Loeches Ignacio I Almirall Jordi J Artigas Antonio A Ignacio Ayestarán Jose J Nuding Sebastian S Ferrer Ricard R Sirgo Rodríguez Gonzalo G Shankar-Hari Manu M Álvarez-Lerma Francisco F Riessen Reimer R Sirvent Josep-Maria JM Kluge Stefan S Zacharowski Kai K Bonastre Mora Juan J Lapp Harald H Wöbker Gabriele G Achtzehn Ute U Brealey David D Kempa Axel A Sánchez García Miguel M Brederlau Jörg J Kochanek Matthias M Reschreiter Henrik Peer HP Wise Matthew P MP Belohradsky Bernd H BH Bobenhausen Iris I Dälken Benjamin B Dubovy Patrick P Langohr Patrick P Mayer Monika M Schüttrumpf Jörg J Wartenberg-Demand Andrea A Wippermann Ulrike U Wolf Daniele D Torres Antoni A
Intensive care medicine 20180409 4
<h4>Purpose</h4>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).<h4>Methods</h4>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 venti ...[more]