Incidence of Sepsis-Induced Coagulopathy (INSIC) Trial: Study Protocol of a Combined Retrospective and Prospective, Multicenter, International, Cross-Sectional, Longitudinal, and Epidemiological Observational Trial

Abstract

Background/Objectives: Sepsis and septic shock are the most severe forms of infection. Due to the intensive cross-talk of the coagulation and immune system, coagulopathies regularly occur in sepsis. The International Society on Thrombosis and Hemostasis refers to these coagulation abnormalities as sepsis-induced coagulopathies (SICs). The presence of SICs can be assessed using the SIC score. In parallel, a score for "sepsis-associated coagulopathy" (SAC) was introduced that, in contrast to the SIC score, allows coagulopathy to be classified according to its severity. In the past, multicenter, randomized controlled trials have repeatedly failed to prove the efficacy of specific therapeutic measures targeting SICs or SACs. This could potentially be explained by insufficient knowledge about the prevalence and incidence of SIC and the rate of spontaneous recovery. The Incidence of Sepsis-Induced Coagulopathy (INSIC) trial is intended to address this problem. Methods: The aim of the INSIC trial is to measure the incidence and prevalence of SIC-in addition to the rate of spontaneous SIC recoveries-during the first days of sepsis treatment to provide a solid base of data for future interventional trials. We aim to include all patients with sepsis treated in any one of 150 participating intensive care units in 100 hospitals located in Austria, Luxembourg, and Germany to determine the prevalence of SIC (on day 1 of the study period as well as on three selected days in the fourth quarter of each year from 2019 to 2024). SIC incidence will be assessed over a 14-day period starting on 10 March 2025. Secondary endpoints are 28-day survival and the occurrence of severe thromboembolic events and bleeding. In addition, each of the aforementioned outcome parameters will be assessed for correlation with the severity classification of the SAC score. Conclusions: The INSIC trial is the first study to determine the prevalence as well as the incidence of SIC, to prospectively examine the course of SIC longitudinally over a 14-day period, and to determine the rate of spontaneous recoveries within 72 h under standard treatment in a large cohort of patients. This information will provide a sound basis for future studies.

Keywords: incidence; prevalence; sepsis; sepsis-induced coagulopathy; septic shock.

Figure 1

Hospital structural data collected from each study center. CRP = C-reactive protein; ICU = intensive care unit, LBP = lipopolysaccharide-binding protein, IL = interleukin; PCT = procalcitonin, SOP = standard operating procedure.

Figure 2

Overview of the timeline of the INSIC trial. SIC = sepsis-induced coagulopathy.