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 (Carl-Neuberg-Str. 1, 30625 Hannover, Germany)
Dellinger, R. Phillip (Cooper Medical School of Rowan University. Department of Medicine)
Ebelt, Henning (Universitätsklinikum Halle (Saale). Klinik und Poliklinik für Innere Medizin III)
Ferrer, Miguel (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Opal, Steven M. (Rhode Island Hospital. Infectious Disease Division)
Singer, Mervyn (University College London. Bloomsbury Institute of Intensive Care Medicine)
Vincent, Jean-Louis (Erasme University Hospital. Department of Intensive Care)
Werdan, Karl (St. James's Hospital. Trinity Centre for Health Sciences)
Martin-Loeches, Ignacio (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Almirall i Pujol, Jordi (Hospital de Mataró. Consorci Sanitari del Maresme)
Artigas Raventós, Antoni (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Ignacio Ayestarán, Jose (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Nuding, Sebastian (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Ferrer, Ricard (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Sirgo Rodríguez, Gonzalo (Hospital Universitari Joan XXIII de Tarragona)
Shankar-Hari, Manu (Guy's and St. Thomas' NHS Foundation Trust. Intensive Care Medicine)
Álvarez Lerma, Francisco (Hospital del Mar (Barcelona, Catalunya))
Riessen, Reimer (Universitätsklinikum Tübingen. Internistische Intensivstation)
Sirvent, Josep-Maria (Hospital Universitari de Girona Doctor Josep Trueta)
Kluge, Stefan (Universitätsklinikum Hamburg-Eppendorf. Klinik für Intensivmedizin)
Zacharowski, Kai (Universitätsklinikum Frankfurt. Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie)
Bonastre Mora, Juan (Hospital Universitari i Politècnic La Fe (València))
Lapp, Harald (Medizinische Klinik, Kardiologie und Intensivmedizin, Helios Klinikum Erfurt, Erfurt, Germany)
Wöbker, Gabriele (Klinik für Intensivmedizin, Helios Universitätsklinikum Wuppertal, Wuppertal, Germany)
Achtzehn, Ute (Klinikum Chemnitz gGmbH. Innere Medizin IV - Pneumologie)
Brealey, David (Critical Care Unit, NIHR University College London Hospitals Biomedical Research Centre, University College London Hospitals, NHS Foundation Trust, London, UK)
Kempa, Axel (Katharinenhospital, Stuttgart. Klinik für Allgemeine Innere Medizin)
Sánchez García, Miguel (Hospital Clínico San Carlos (Madrid))
Brederlau, Jörg (Helios Klinikum Berlin-Buch, Klinik für Intensivmedizin)
Kochanek, Matthias (University Hospital of Cologne. Department I of Internal Medicine)
Reschreiter, Henrik Peer (Poole Hospital NHS Foundation Trust)
Wise, Matthew P. (Heath Park, Cardiff)
Belohradsky, Bernd H. (University Children's Hospital Munich)
Bobenhausen, Iris (Biotest AG)
Dälken, Benjamin (Biotest AG)
Dubovy, Patrick (Biotest AG)
Langohr, Patrick (Biotest AG)
Mayer, Monika (Biotest AG)
Schüttrumpf, Jörg (Biotest AG)
Wartenberg-Demand, Andrea (Biotest AG)
Wippermann, Ulrike (Biotest AG)
Wolf, Daniele (Biotest AG)
Torres, Antoni (Hospital Clínic i Provincial de Barcelona)

Data:	2018
Resum:	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). 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). 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. 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. The online version of this article (10. 1007/s00134-018-5143-7) contains supplementary material, which is available to authorized users.
Nota:	Altres ajuts: Professional medical writing assistance was provided by Fiona Boswell, PhD, and editorial assistance was provided by Katie Lay, MSc, at Caudex (Oxford, UK), funded by Biotest AG. Accovion GmbH, Eschborn, Germany (now Clinipace Worldwide, Morrisville, North Carolina, USA) provided study management services. We would like to thank all centers and staff involved in this study, and the patients and their families. Bernd H. Belohradsky, V. Marco Ranieri (Chair), Richard Strauss, and Gerhard W. Sybrecht monitored patient safety and data integrity as members of the DSMB.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Trimodulin ; Polyclonal antibody ; Severe community-acquired pneumonia ; Add-on therapy ; Immunoglobulin M
Publicat a:	Intensive Care Medicine, Vol. 44 (april 2018) , p. 438-448, ISSN 1432-1238

DOI: 10.1007/s00134-018-5143-7
PMID: 29632995

11 p, 838.8 KB

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