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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)

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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). / Welte, Tobias; Dellinger, R Phillip; Ebelt, Henning; Ferrer, Miguel; Opal, Steven M; Singer, Mervyn; Vincent, Jean-Louis; Werdan, Karl; Martin-Loeches, Ignacio; Almirall, Jordi; Artigas, Antonio; Ignacio Ayestarán, Jose; Nuding, Sebastian; Ferrer, Ricard; Sirgo Rodríguez, Gonzalo; Shankar-Hari, Manu; Álvarez-Lerma, Francisco; Riessen, Reimer; Sirvent, Josep-Maria; Kluge, Stefan; Zacharowski, Kai; Bonastre Mora, Juan; Lapp, Harald; Wöbker, Gabriele; Achtzehn, Ute; Brealey, David; Kempa, Axel; Sánchez García, Miguel; Brederlau, Jörg; Kochanek, Matthias; Reschreiter, Henrik Peer; Wise, Matthew P; Belohradsky, Bernd H; Bobenhausen, Iris; Dälken, Benjamin; Dubovy, Patrick; Langohr, Patrick; Mayer, Monika; Schüttrumpf, Jörg; Wartenberg-Demand, Andrea; Wippermann, Ulrike; Wolf, Daniele; Torres, Antoni.

in: INTENS CARE MED, Jahrgang 44, Nr. 4, 04.2018, S. 438-448.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Welte, T, Dellinger, RP, Ebelt, H, Ferrer, M, Opal, SM, Singer, M, Vincent, J-L, Werdan, K, Martin-Loeches, I, Almirall, J, Artigas, A, Ignacio Ayestarán, J, Nuding, S, Ferrer, R, Sirgo Rodríguez, G, Shankar-Hari, M, Álvarez-Lerma, F, Riessen, R, Sirvent, J-M, Kluge, S, Zacharowski, K, Bonastre Mora, J, Lapp, H, Wöbker, G, Achtzehn, U, Brealey, D, Kempa, A, Sánchez García, M, Brederlau, J, Kochanek, M, Reschreiter, HP, Wise, MP, Belohradsky, BH, Bobenhausen, I, Dälken, B, Dubovy, P, Langohr, P, Mayer, M, Schüttrumpf, J, Wartenberg-Demand, A, Wippermann, U, Wolf, D & Torres, A 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)', INTENS CARE MED, Jg. 44, Nr. 4, S. 438-448. https://doi.org/10.1007/s00134-018-5143-7

APA

Welte, T., Dellinger, R. P., Ebelt, H., Ferrer, M., Opal, S. M., Singer, M., Vincent, J-L., Werdan, K., Martin-Loeches, I., Almirall, J., Artigas, A., Ignacio Ayestarán, J., Nuding, S., Ferrer, R., Sirgo Rodríguez, G., Shankar-Hari, M., Álvarez-Lerma, F., Riessen, R., Sirvent, J-M., ... Torres, A. (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). INTENS CARE MED, 44(4), 438-448. https://doi.org/10.1007/s00134-018-5143-7

Vancouver

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). INTENS CARE MED. 2018 Apr;44(4):438-448. https://doi.org/10.1007/s00134-018-5143-7

Bibtex

@article{bed16e29c4604b70a874ff931e90588e,
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)",
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 = "Journal Article",
author = "Tobias Welte and Dellinger, {R Phillip} and Henning Ebelt and Miguel Ferrer and Opal, {Steven M} and Mervyn Singer and Jean-Louis Vincent and Karl Werdan and Ignacio Martin-Loeches and Jordi Almirall and Antonio Artigas and {Ignacio Ayestar{\'a}n}, Jose and Sebastian Nuding and Ricard Ferrer and {Sirgo Rodr{\'i}guez}, Gonzalo and Manu Shankar-Hari and Francisco {\'A}lvarez-Lerma and Reimer Riessen and Josep-Maria Sirvent and Stefan Kluge and Kai Zacharowski and {Bonastre Mora}, Juan and Harald Lapp and Gabriele W{\"o}bker and Ute Achtzehn and David Brealey and Axel Kempa and {S{\'a}nchez Garc{\'i}a}, Miguel and J{\"o}rg Brederlau and Matthias Kochanek and Reschreiter, {Henrik Peer} and Wise, {Matthew P} and Belohradsky, {Bernd H} and Iris Bobenhausen and Benjamin D{\"a}lken and Patrick Dubovy and Patrick Langohr and Monika Mayer and J{\"o}rg Sch{\"u}ttrumpf and Andrea Wartenberg-Demand and Ulrike Wippermann and Daniele Wolf and Antoni Torres",
year = "2018",
month = apr,
doi = "10.1007/s00134-018-5143-7",
language = "English",
volume = "44",
pages = "438--448",
journal = "INTENS CARE MED",
issn = "0342-4642",
publisher = "Springer",
number = "4",

}

RIS

TY - JOUR

T1 - 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)

AU - Welte, Tobias

AU - Dellinger, R Phillip

AU - Ebelt, Henning

AU - Ferrer, Miguel

AU - Opal, Steven M

AU - Singer, Mervyn

AU - Vincent, Jean-Louis

AU - Werdan, Karl

AU - Martin-Loeches, Ignacio

AU - Almirall, Jordi

AU - Artigas, Antonio

AU - Ignacio Ayestarán, Jose

AU - Nuding, Sebastian

AU - Ferrer, Ricard

AU - Sirgo Rodríguez, Gonzalo

AU - Shankar-Hari, Manu

AU - Álvarez-Lerma, Francisco

AU - Riessen, Reimer

AU - Sirvent, Josep-Maria

AU - Kluge, Stefan

AU - Zacharowski, Kai

AU - Bonastre Mora, Juan

AU - Lapp, Harald

AU - Wöbker, Gabriele

AU - Achtzehn, Ute

AU - Brealey, David

AU - Kempa, Axel

AU - Sánchez García, Miguel

AU - Brederlau, Jörg

AU - Kochanek, Matthias

AU - Reschreiter, Henrik Peer

AU - Wise, Matthew P

AU - Belohradsky, Bernd H

AU - Bobenhausen, Iris

AU - Dälken, Benjamin

AU - Dubovy, Patrick

AU - Langohr, Patrick

AU - Mayer, Monika

AU - Schüttrumpf, Jörg

AU - Wartenberg-Demand, Andrea

AU - Wippermann, Ulrike

AU - Wolf, Daniele

AU - Torres, Antoni

PY - 2018/4

Y1 - 2018/4

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1007/s00134-018-5143-7

DO - 10.1007/s00134-018-5143-7

M3 - SCORING: Journal article

C2 - 29632995

VL - 44

SP - 438

EP - 448

JO - INTENS CARE MED

JF - INTENS CARE MED

SN - 0342-4642

IS - 4

ER -