Abstract
BackgroundPeritonitis 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/designA 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.DiscussionThis 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 registrationEudraCT, 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).
Highlights
Peritonitis is responsible for thousands of deaths annually in Germany alone
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, possibly opening the way to a personalized medicine
As peritonitis can rapidly lead to bacteremia and sepsis, infectious source control and antibiotic treatment remain the methods of choice to limit the spread of bacteria and the secretion of their toxins
Summary
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. Peritonitis is classified as follows [2]: primary (hematogenic in children, bacterial in adults, or following tuberculosis or gonorrhea); secondary (post-operative, post-traumatic, or due to perforation); tertiary (owing to immune deficiency, usually avirulent); quaternary (due to intra-abdominal abscess, or hospital-acquired or catheter-associated infection); and specific forms due, e.g., to Candida infection or chemical effects. As peritonitis can rapidly lead to bacteremia and sepsis, infectious source control and antibiotic treatment remain the methods of choice to limit the spread of bacteria and the secretion of their toxins. Even after source control and adequate antibiotic treatment, severe sepsis or septic shock can occur, so that the lethality associated with peritonitis is still high and, despite all medical progress, has hardly been reduced in the past 20 years. With an overall mortality rate between 30% and 40% depending upon the population observed, (post-operative) secondary peritonitis remains one of the deadliest diseases in the intensive care unit (ICU) [3]
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