title: Concept for a study design in patients with severe community-acquired pneumonia: A randomised controlled trial with a novel IGM-enriched immunoglobulin preparation - The CIGMA study.
abstract: BACKGROUND
  Severe community-acquired pneumonia is defined as community-acquired pneumonia that requires intensive medical care. Mortality in these patients is still high depending on time and admission. Since bad outcomes may occur despite antibiotic therapy to treat severe community-acquired pneumonia, the focus has shifted to targeting the host response. The CIGMA Study examines the safety and efficacy of the novel IgM-enriched immunoglobulin preparation BT086 when added to standard of care treatment.
  
  
  METHODS
  The aim of this multicentre, randomised, placebo-controlled, double-blind, parallel-group, adaptive group-sequential phase II study is to determine the efficacy and safety of BT086, an IgM-enriched immunoglobulin preparation, as an adjunctive treatment in mechanically-ventilated patients with severe community-acquired pneumonia. The increase of ventilator-free days is the primary endpoint in this study. For this trial, ventilator-free days are defined as the number of days between successful extubation from endotracheal ventilation and day 28 after enrolment of the patient into the study. Two interim analyses were considered for this study.
  
  
  CONCLUSIONS
  Several novel agents for treatment of sepsis have been evaluated in the last two decades; however, none has significantly reduced mortality rates. Failure was attributed to the heterogeneity of septic patients or sepsis. Severe community-acquired pneumonia was chosen as the indication for this study to increase homogeneity within this patient population.
  
  
  BACKGROUND
  EUDRACT 2010-022380-35.
authors.affiliation: Hannover Medical School, Clinic for Pneumology and German Center of Lung Research (DZL), Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: Welte.Tobias@mh-hannover.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.affiliation: Cooper Medical School of Rowan University, Camden, NJ 08103, USA.
authors.forename: R Phillip
authors.initials: RP
authors.lastname: Dellinger
authors.affiliation: St. Johann Nepomuk Hospital, Haarbergstr. 72, 99097 Erfurt, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Ebelt
authors.affiliation: Servei de Pneumologia, Hospital Clínic de Barcelona, IDIBAPS, CibeRes (CB06/06/0028). Villarroel 170, 08036 Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Ferrer
authors.affiliation: Infectious Disease Division, Alpert Medical School of Brown University, Providence, RI 02860, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Opal
authors.affiliation: Corporate Clinical Research Biotest AG, Landsteinerstr. 5, 63303 Dreieich, Germany.
authors.forename: Dorothee E
authors.initials: DE
authors.lastname: Schliephake
authors.affiliation: Corporate Clinical Research Biotest AG, Landsteinerstr. 5, 63303 Dreieich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wartenberg-Demand
authors.affiliation: Department of Medicine, University Hospital Halle (Saale), Martin-Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, D-06120 Halle (Saale), Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Werdan
authors.affiliation: Accovion GmbH, Helfmann-Park 10, D-65760 Eschborn, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Löffler
authors.affiliation: Servei de Pneumologia, Hospital Clínic de Barcelona, Villarroel 170, 08036 Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Torres
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017714:Community-Acquired Infections / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D007075:Immunoglobulin M / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D016896:Treatment Outcome; D015300:Ventilator Weaning / Q000379:methods
chemical_list: D007075:Immunoglobulin M
keywords: Adjunctive therapy; BT086; IgM-enriched immunoglobulins; Mechanically-ventilated; Severe community-acquired pneumonia; Ventilator-free days