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, Vol. 44, No. 4, 04.2018, p. 438-448.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -