Welte, Tobias, Dellinger, R. Phillip, Ebelt, Henning, Ferrer, Miguel ORCID: 0000-0001-8171-6673, Opal, Steven M., Singer, Mervyn ORCID: 0000-0002-1042-6350, Vincent, Jean-Louis ORCID: 0000-0001-6011-6951, Werdan, Karl, Martin-Loeches, Ignacio, Almirall, Jordi ORCID: 0000-0002-3821-4341, Artigas, Antonio, Ignacio Ayestaran, Jose, Nuding, Sebastian, Ferrer, Ricard ORCID: 0000-0002-4859-4747, Sirgo Rodriguez, Gonzalo, Shankar-Hari, Manu ORCID: 0000-0002-5338-2538, Alvarez-Lerma, Francisco, Riessen, Reimer, Sirvent, Josep-Maria, Kluge, Stefan, Zacharowski, Kai ORCID: 0000-0002-0212-9110, Bonastre Mora, Juan, Lapp, Harald, Woebker, Gabriele, Achtzehn, Ute, Brealey, David, Kempa, Axel, Sanchez Garcia, Miguel, Brederlau, Joerg, Kochanek, Matthias, Reschreiter, Henrik Peer, Wise, Matthew P., Belohradsky, Bernd H., Bobenhausen, Iris, Dalken, Benjamin, Dubovy, Patrick, Langohr, Patrick, Mayer, Monika, Schuettrumpf, Joerg, Wartenberg-Demand, Andrea, Wippermann, Ulrike, Wolf, Daniele and Torres, Antoni ORCID: 0000-0002-8643-2167 (2018). 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., 44 (4). S. 438 - 449. NEW YORK: SPRINGER. ISSN 1432-1238

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Abstract

Purpose: The CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing similar to 23% immunoglobulin (Ig) M, similar to 21% IgA, and similar to 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Welte, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dellinger, R. PhillipUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ebelt, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferrer, MiguelUNSPECIFIEDorcid.org/0000-0001-8171-6673UNSPECIFIED
Opal, Steven M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Singer, MervynUNSPECIFIEDorcid.org/0000-0002-1042-6350UNSPECIFIED
Vincent, Jean-LouisUNSPECIFIEDorcid.org/0000-0001-6011-6951UNSPECIFIED
Werdan, KarlUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin-Loeches, IgnacioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Almirall, JordiUNSPECIFIEDorcid.org/0000-0002-3821-4341UNSPECIFIED
Artigas, AntonioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ignacio Ayestaran, JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuding, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferrer, RicardUNSPECIFIEDorcid.org/0000-0002-4859-4747UNSPECIFIED
Sirgo Rodriguez, GonzaloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shankar-Hari, ManuUNSPECIFIEDorcid.org/0000-0002-5338-2538UNSPECIFIED
Alvarez-Lerma, FranciscoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riessen, ReimerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sirvent, Josep-MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kluge, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zacharowski, KaiUNSPECIFIEDorcid.org/0000-0002-0212-9110UNSPECIFIED
Bonastre Mora, JuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lapp, HaraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woebker, GabrieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Achtzehn, UteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brealey, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kempa, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanchez Garcia, MiguelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brederlau, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kochanek, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reschreiter, Henrik PeerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wise, Matthew P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belohradsky, Bernd H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bobenhausen, IrisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dalken, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dubovy, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langohr, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayer, MonikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuettrumpf, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wartenberg-Demand, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wippermann, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, DanieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Torres, AntoniUNSPECIFIEDorcid.org/0000-0002-8643-2167UNSPECIFIED
URN: urn:nbn:de:hbz:38-189984
DOI: 10.1007/s00134-018-5143-7
Journal or Publication Title: Intensive Care Med.
Volume: 44
Number: 4
Page Range: S. 438 - 449
Date: 2018
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1432-1238
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
C-REACTIVE PROTEIN; ADJUNCTIVE THERAPIES; IGM; IMMUNOGLOBULINS; PROCALCITONIN; INFECTION; SEPSIS; MARKER; ADULTS; MODELMultiple languages
Critical Care MedicineMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18998

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