TY - JOUR A1 - Kalvelage, Christina A1 - Zacharowski, Kai A1 - Bauhofer, Artur A1 - Gockel, Ulrich A1 - Adamzik, Michael A1 - Nierhaus, Axel A1 - Kujath, Peter A1 - Eckmann, Christian A1 - Pletz, Mathias Wilhelm Rudolf A1 - Bracht, Hendrik A1 - Simon, Tim-Philipp A1 - Winkler, Michael A1 - Kindgen-Milles, Detlef A1 - Albertsmeier, Markus A1 - Weigand, Markus A1 - Ellger, Björn A1 - Ragaller, Maximilian A1 - Ullrich, Roman A1 - Marx, Gernot T1 - Personalized medicine with IgGAM compared with standard of care for treatment of peritonitis after infectious source control (the PEPPER trial) : study protocol for a randomized controlled trial T2 - Trials N2 - Background: Peritonitis is responsible for thousands of deaths annually in Germany alone. Even source control (SC) and antibiotic treatment often fail to prevent severe sepsis or septic shock, and this situation has hardly improved in the past two decades. Most experimental immunomodulatory therapeutics for sepsis have been aimed at blocking or dampening a specific pro-inflammatory immunological mediator. However, the patient collective is large and heterogeneous. There are therefore grounds for investigating the possibility of developing personalized therapies by classifying patients into groups according to biomarkers. This study aims to combine an assessment of the efficacy of treatment with a preparation of human immunoglobulins G, A, and M (IgGAM) with individual status of various biomarkers (immunoglobulin level, procalcitonin, interleukin 6, antigen D-related human leucocyte antigen (HLA-DR), transcription factor NF-κB1, adrenomedullin, and pathogen spectrum). Methods/design: A total of 200 patients with sepsis or septic shock will receive standard-of-care treatment (SoC). Of these, 133 patients (selected by 1:2 randomization) will in addition receive infusions of IgGAM for 5 days. All patients will be followed for approximately 90 days and assessed by the multiple-organ failure (MOF) score, by the EQ QLQ 5D quality-of-life scale, and by measurement of vital signs, biomarkers (as above), and survival. Discussion: This study is intended to provide further information on the efficacy and safety of treatment with IgGAM and to offer the possibility of correlating these with the biomarkers to be studied. Specifically, it will test (at a descriptive level) the hypothesis that patients receiving IgGAM who have higher inflammation status (IL-6) and poorer immune status (low HLA-DR, low immunoglobulin levels) have a better outcome than patients who do not receive IgGAM. It is expected to provide information that will help to close the knowledge gap concerning the association between the effect of IgGAM and the presence of various biomarkers, thus possibly opening the way to a personalized medicine. Trial registration: EudraCT, 2016–001788-34; ClinicalTrials.gov, NCT03334006. Registered on 17 Nov 2017. Trial sponsor: RWTH Aachen University, represented by the Center for Translational & Clinical Research Aachen (contact Dr. S. Isfort). KW - Personalized medicine KW - Biomarkers KW - Pentaglobin KW - IgGAM KW - Sepsis KW - Peritonitis KW - Severe bacterial infection Y1 - 2019 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/48961 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-489611 SN - 1468-6694 SN - 1745-6215 SN - 1468-6708 N1 - Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. VL - 20 IS - 1, Art. 156 SP - 1 EP - 10 PB - BioMed Central CY - London ER -