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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)Open access

Tobias Welte| R. Phillip Dellinger| Henning Ebelt| Miguel Ferrer| Steven M. Opal| Mervyn Singer| Jean-Louis Vincent| Karl Werdan| Ignacio Martin-Loeches| Jordi Almirall| Antonio Artigas| Jose Ignacio Ayestarán| Sebastian Nuding| Ricard Ferrer| Gonzalo Sirgo Rodríguez| Manu Shankar-Hari| Francisco Álvarez-Lerma| Reimer Riessen| Josep-Maria Sirvent| Stefan Kluge| Kai Zacharowski| Juan Bonastre Mora|
Seven-Day Profile Publication
Volume 44, Issue 4 / April , 2018

Pages 438 - 448

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.

Keywords

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