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

Autor: Christian Eckmann, Michael Adamzik, Artur Bauhofer, Michael Winkler, Kai Zacharowski, Tim-Phillip Simon, Markus A. Weigand, Christina Kalvelage, Gernot Marx, Axel Nierhaus, Maximilian Ragaller, Roman Ullrich, Maekus Albertsmeier, Peter Kujath, Hendrik Bracht, Mathias W. Pletz, Detlef Kindgen-Milles, Ulrich Gockel, Björn Ellger
Rok vydání: 2018
Předmět:
Time Factors
Medicine (miscellaneous)
Procalcitonin
law.invention
Severe bacterial infection
Study Protocol
610 Medical sciences Medicine
0302 clinical medicine
Randomized controlled trial
law
Germany
Multicenter Studies as Topic
Pharmacology (medical)
Prospective Studies
030212 general & internal medicine
Precision Medicine
Infusions
Intravenous
Randomized Controlled Trials as Topic
lcsh:R5-920
Immunoglobulins
Intravenous
Anti-Bacterial Agents
ddc
Treatment Outcome
Austria
Immunotherapy
lcsh:Medicine (General)
medicine.medical_specialty
Randomization
Clinical Decision-Making
Vital signs
Peritonitis
Sepsis
03 medical and health sciences
Predictive Value of Tests
Internal medicine
medicine
Humans
ddc:610
Septic shock
business.industry
Patient Selection
Pentaglobin
medicine.disease
Personalized medicine
IgGAM
Immunoglobulin A
Clinical research
Immunoglobulin M
Immunoglobulin G
business
Biomarkers
030217 neurology & neurosurgery
Zdroj: Trials
Trials 20(1), 156 (2019). doi:10.1186/s13063-019-3244-4
Trials, Vol 20, Iss 1, Pp 1-10 (2019)
DOI: 10.1186/s13063-019-3244-4
Popis: 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). Electronic supplementary material The online version of this article (10.1186/s13063-019-3244-4) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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