Clinical trial for sepsis patients

Clinical trial to investigate the new strategy for sepsis

- For saving the life –

By Masayuki Akatsuka
Department of Intensive Care Medicine, Sapporo Medical University School of Medicine

About This Project

Sepsis is a complex disorder that develops from a dysregulated host response to infection, leading to the dysfunction of multiple organs and an increased risk of death in the intensive care unit. The number of cases is increasing worldwide due to the aging population, and updating treatment strategies is an urgent task.

We will conduct randomized clinical trial to test the hypothesis that immunoglobulin (IVIG) therapy is beneficial in sepsis patients with hypogammaglobulinemia.  

 What is the context of this research?

Previous studies have reported that patients with severe infections heve hypogammaglobulinemia due to suppression and leakage of immunoglobulins (1). It has also been reported that serum IgG levels at the time of admission to the ICU is related to the severity and mortality (2). Therefore, we investigated the relationship between hypogammaglobulinemia and the outcome of sepsis patients in the ICU at our hospital and derived a cutoff value for serum IgG levels that indicate poor prognosis. It was pointed out that serum IgG levels below 670 mg/dL are associated with an increase in 28-day mortality (3). Furthermore, using the derived cutoff value for serum IgG, we compared data from patients admitted to the ICU at our hospital between the group of sepsis patients with hypogammaglobulinemia (serum IgG level less than 670 mg/dL) who received IVIG therapy and the group who did not receive IVIG therapy. We found that IVIG administration in patients with sepsis and low serum IgG levels was associated with improved prognosis (4).

  What is the significance of this project?

Various previous studies have pointed out the possibility that IVIG therapy for sepsis patients with hypogammaglobulinemia may improve mortality rates, but the issue is that the level of evidence is low due to the study design. Therefore, we have planned the randomized controlled trial with higher level of evidence. This project would lead to the significant results for the future management of sepsis patients.

   What are the goals of the project?

Sepsis, which is accompanied by low serum IgG levels from the early stage of the onset due to suppressed production, leakage, and consumption, is thought to be caused by increased antibody consumption due to infection and extravasation of IgG due to increased vascular permeability. Previous studies have reported that mortality rates increase when the SOFA score is less than 8 and serum IgG levels are below 407 mg/dL (5). Based on these findings, it is thought that it may be meaningful to administer IVIG considering the absolute deficiency of antibodies, and we have launched a study to verify the hypothesis that "IVIG therapy is beneficial in sepsis patients with hypogammaglobulinemia." 

✔︎ How to back this project: English Guide

 Project Timeline

References

(1) Taccone FS, Stordeur P, De Backer D, Creteur J, Vincent JL. Gamma-globulin levels in patients with community-acquired septic shock. Shock. 2009 Oct;32(4):379-85. doi: 10.1097/SHK.0b013e3181a2c0b2.
(2) Venet F, Gebeile R, Bancel J, Guignant C, Poitevin-Later F, et al. Assessment of plasmatic immunoglobulin G, A and M levels in septic shock patients. Int Immunopharmacol. 2011 Dec;11(12):2086-90. doi: 10.1016/j.intimp.2011.08.024.
(3) Akatsuka M, Tatsumi H, Sonoda T, Masuda Y. Low immunoglobulin G level is associated with poor outcomes in patients with sepsis and septic shock. J Microbiol Immunol Infect. 2021 Aug;54(4):728-732. doi: 10.1016/j.jmii.2020.08.013.
(4) Akatsuka M, Masuda Y, Tatsumi H, Sonoda T. Efficacy of Intravenous Immunoglobulin Therapy for Patients With Sepsis and Low Immunoglobulin G Levels: A Single-Center Retrospective Study. Clin Ther. 2022 Feb;44(2):295-303. doi: 10.1016/j.clinthera.2021.12.008.
(5) Martin-Loeches I, Muriel-Bombín A, Ferrer R, Artigas A, Sole-Violan J, F, et al. The protective association of endogenous immunoglobulins against sepsis mortality is restricted to patients with moderate organ failure. Ann Intensive Care. 2017 Dec;7(1):44. doi: 10.1186/s13613-017-0268-3.