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135 active trials for Septic Shock

Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. It is the most expensive healthcare condition to treat in United States and has a mortality rate of nearly 30%. It is widely known that exaggerated inflammation and imbalance between sympathetic and parasympathetic arms of the autonomic nervous system (ANS) contribute to progression and adverse outcomes in sepsis. The role of unchecked inflammation and unregulated ANS as a potential treatment target is an important gap in our knowledge that should be explored. Cholinergic anti-inflammatory pathway (CAP) is an intricate network where the ANS senses inflammation by vagus nerve afferents and tries to regulate it by vagus nerve efferents to the reticuloendothelial system. The central hypothesis of this pilot clinical trial is that transcutaneous vagus nerve stimulation (TVNS) at tragus of the external ear can activate the CAP to suppress inflammation and improve autonomic imbalance as measured by inflammatory cytokine levels and heart rate variability (HRV) analysis. The investigators plan to randomize patients with septic shock into active and sham stimulation groups and study the effects of vagal stimulation on inflammatory cytokines, HRV and a clinical severity score of sepsis. Both groups will continue to receive the standard of care treatment for sepsis irrespective of group assignments. The investigators hypothesize that 4 hours of TVNS will suppress inflammatory markers and improve the balance between sympathetic and parasympathetic arms of ANS as measured by HRV, resulting in improved Sequential Organ Failure Assessment Score (SOFA). The preliminary data generated from this pilot study will lay the foundation for a larger clinical trial.

Start: November 2020
Assessment of Microcirculatory Dysfunction in Septic Shock Patients by OCTA

Purpose and rationale: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis and septic shock are major public health problems killing one in every three patients. Microcirculatory dysfunction is frequent in septic shock. The duration and severity of this dysfunction have a prognostic impact by being associated with organ failure and mortality. Our study purposes to demonstrate the feasibility of optical coherence tomography angiography (OCTA) to improve assessment of microcirculatory dysfunction by showing that retinal and choroidal microcirculatory changes with prognostic impact are present during septic shock. Primary objective: To characterize the alterations of retinal and choroidal microcirculation in septic shock. We will test the hypothesis that retinal and/or choroidal microcirculation shows dysfunctional changes (lower vascular density, lower percentage of perfused small vessel, lower blood flow index and higher vascular heterogeneity) in septic shock patients. Secondary objective: To test the prognostic value of retinal and choroidal microcirculatory dysfunction in septic shock. We will test the hypothesis that higher magnitude and persistence of retinal and/or choroidal microcirculatory dysfunction beyond the successful macro-hemodynamic resuscitation are independent predictors of organ failure and mortality in septic shock patients. Study type: Two sequential observational studies. Study design: A cross-sectional case-control study followed by a prospective cohort study with a 90-days longitudinal follow-up period. Study population: 165 septic shock patients and 30 healthy controls. Study duration: 90 days from enrolment to final follow-up assessment. One to two years of enrolment.

Start: February 2021
Study Assessing Efficacy of Plasmatherapy in Septic Shock-induced Coagulopathy: Feasibility Study

No randomized controlled trial (RCT) has investigated the effect of prophylactic fresh frozen plasma (FFP) transfusion in septic or critically ill patients with coagulation abnormalities. The last Surviving Sepsis Campaign therefore suggests with a very low quality of evidence "against the use of fresh frozen plasma during septic shock to correct clotting abnormalities in the absence of bleeding or planned invasive procedures". However, expert opinion highlights that FFP should be transfused "when there is a documented deficiency of coagulation factors (increased prothrombin time, international normalized ratio - INR, or partial thromboplastin time) and the presence of active bleeding or before surgical or invasive procedures". Disseminated intravascular coagulation (DIC) is responsible for such a severe deficiency of coagulation factors. Supplementing the intense deficit of coagulation factors with plasma containing non-activated coagulation factors is therefore a rational therapy in DIC patients. OctaplasLG® is a donor plasma product, with unique features compared to standard fresh frozen plasma: standardized concentrations of natural pro-/anti-coagulation factors; a standardized volume; pathogen free. OctaplasLG® should reduce the "inflammatory hit" on the endothelium, including the glycocalyx, by having standardized levels of coagulation proteins, which can give more sustainable support to the endothelial regeneration as compared to standard fresh frozen plasma.

Start: September 2020
Optimization of Sepsis Therapy Based on Patient-specific Digital Precision Diagnostics

Sepsis is triggered by an infection and represents one of the greatest challenges of modern intensive care medicine. With regard to a targeted antimicrobial treatment strategy, the earliest possible pathogen detection is of crucial importance. Until now, culture-based detection methods represent the diagnostic gold standard, although they are characterized by numerous limitations. Culture-independent molecular diagnostic procedures may represent a promising alternative. In particular, the concept of plasmatic detection of circulating, free DNA employing next-generation sequencing (NGS) has shown to be suitable for the detection of disease-causing pathogens in patients with bloodstream infections. The DigiSep-Trial is a randomized, controlled, interventional, multicenter trial to characterize the effect of the combination of NGS-based digital precision diagnostics, standard-of-care microbiological analyses and optional expert exchanges compared to solely standard-of-care microbiological analyses in the clinical picture of sepsis / septic shock. The study examines in 410 patients (n = 205 per arm) with sepsis / septic shock whether the so-called DOOR-RADAR (Desirability of Outcome Ranking / Response Adjusted for Duration of Antibiotic Risk) score (representing a combined endpoint including the criteria (1) inpatient admission time, (2) consumption of antibiotics, (3) mortality and (4) acute renal failure (ARF)) can be significantly improved, by application of an additional NGS-based diagnostic concept. We also aim to investigate whether the new diagnostic procedure is cost-effective. It is postulated that the inpatient admission time, mortality rate, incidence of ARF, the duration of antimicrobial therapy as well as the costs of complications and outpatient aftercare can be reduced. Moreover, a significant improvement in the quality of life (QoL) of the affected patients can be expected. Extensive preparatory work suggests that NGS-based diagnostics have higher specificity and sensitivity compared to standard-of-care microbiological analyses for detecting bloodstream infections. This preliminary work for the DigiSep-Trial with the help of an interventional study design provides the optimal basis to establish this new concept as part of the national standard based on the best possible evidence.

Start: January 2022