View clinical trials related to Sepsis.
Filter by:Surgical trauma elicits an immune response aiming to initiate healing and remove debris and damaged tissue locally at the wound site (1). This local reaction includes a considerable production of cytokines and chemokines that enters the circulation and initiate a systemic inflammatory response mediated by circulating cytokines and chemokines. This response is called systemic inflammatory immune response (SIRS) and is an aseptic systemic inflammation. Postoperative inflammation produces proinflammatory cytokines, mainly IL-6, IL1 beta, and tumor necrosis factor alfa (2). Neutrophils and emergency granulopoesis Polymorphonuclear neutrophils constitute the most abundant population of white blood cells. Their main task is to provide innate immune protection of the host from microbial attack, migrating to the site of infection, engulfing the microbes by phagocytosis, and killing the prey through attack by reactive oxygen species (ROS) and antimicrobial granule pro¬teins (22). Upon systemic infection or inflammation, e.g., sepsis or trauma, the bone marrow enters a state of emergency granulopoiesis, drenched in cytokines that augment production and survival of neutrophils for rapid delivery to the blood (23-25). Recently, advanced techniques have evolved that al¬low the isolation of different developmental stages of steady-state and emergency neutrophils, and characterization of these has just begun (26). Glycans Glycans (polysaccharides) attached to proteins and lipids on the surfaces on immune cells serve as ligands for glycan-binding proteins, lectins. Several neutrophil processes are directed by gly¬can - lectin interactions; selectin-directed rolling on the endothelium, siglec-mediated in¬hibitory signals, and activation of effector function by galectins. Many of the proteins that end up in neutrophil intra-cellular granules are highly glycosylated, but not much is known about if and how the neutrophil glycome evolves during the 'targeting-by-timing' process of differentiation and how this is affected by emergency granulopoiesis during systemic infection and inflammation. Here is a clear knowledge gap.
Background: Despite management improvement in lasts years, S.aureus bacteremia leads to high morbidity and mortality. For over 50 years, methicillin-susceptible S.aureus (MSSA) bacteremia standard treatment was cloxacillin. Previous studies using different therapies and combination treatment fall to improve survival in these patients. Aim: to demonstrate the efficacy of the cloxacillin and fosfomycin combination administered during the first week of treatment, compared with cloxacillin monotherapy in patients with MSSA bacteremia in treatment success. Methods: A multicentre, superiority, open-label, randomized, phase IV-III, two-armed parallel (1:1) groups clinical trial. Adult patients with MSSA bacteremia will be randomized to Combination therapy group: patients will receive intravenous cloxacillin 2g/4h and fosfomycin 3 g/6h for the duration of 7 days treatment, or Standard therapy group: patients will receive intravenous cloxacillin 2g/4h for the duration of 7 days IV treatment. After the first week, antibiotic treatment and duration will be decided by responsible clinician following clinical practice. The primary endpoint is the treatment success measured at day 7 of treatment; a composite endpoint defined by all of the following criteria met after randomization: patient alive at day 7 AND stable or improved quick SOFA score (compared with baseline) at day 7 AND fever resolved at day 7 AND negative blood cultures for S. aureus at day 7. In case of achieving statistical differences in the primary endpoint, investigators will perform a hierarchical analysis of the treatment success at Test of Cure visit (TOC, 12 weeks after randomization), defined by the presence of all of the following: patient alive at TOC AND no evidence of microbiological treatment failure defined as isolation of S. aureus from blood culture or other sterile site from day 8 after randomization until TOC. Investigators have assumed a 74% of treatment success in monotherapy group. Accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 183 subjects are necessary in first group and 183 in the second to find a statistically significant difference of 12%. It has been anticipated a drop-out rate of 5%. Discussion: Randomized studies assessing efficacy of different treatment in MSSA bacteremia are lacking. This study could help to improve knowledge about MSSA bacteremia and whether combined treatment with cloxacillin and fosfomycin could improve outcomes compared with standard treatment.
This phase II trial studies how well early metabolic resuscitation therapy works in reducing multi-organ dysfunction in patients with septic shock. Early metabolic resuscitation is made of large doses of glucose, protein, and essential metabolic molecules that may help lower the effects of septic shock on the body. Giving patients early metabolic resuscitation in combination with standard of care may work better in reducing multi-organ dysfunction syndrome in patients with septic shock compared to standard of care alone.
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Early during sepsis course, immature neutrophils could be found in the bloodstream and may be less efficient than mature neutrophils in reactive oxygen species (ROS) production. ROS induce an oxidative stress for bacteria which can protect through the SOS response. The main objective is to evaluate the level of ROS produced in the early steps of sepsis by the immature neutrophils.
This phase II randomized study will assess the effect of receiving IV recombinant human IL-7 (CYT107) versus placebo in lymphopenic sepsis patients The aim is to confirm the immune cell reconstitution observed in other studies and other patient populations among which the IRIS-7 A&B study which was conducted in the same patient population.
This study will investigate the metabolic alterations of vascular cells caused by sepsis and septic shock
Patients admitted to the Intensive Care Unit after severe injury are prone to suffer from infectious complications and even sepsis. Despite tremendous efforts the etiology of this increased susceptibility to infectious pathogens is incompletely understood. Clinical signs and symptoms as well as current diagnostic clinical tests (WBC, CRP, cytokines, interleukines) lack sensitivity or specificity for adequate prediction of the development of infectious complications or sepsis. Neutrophil granulocytes, cells of the innate immune system, play an important role in the defence against invading bacterial pathogens and are crucial in preventing fulminant infections. For successful eradication of a bacterium neutrophils need to exert specific functions: chemotaxis, migration, phagocytosis, degranulation and production of radical oxygen species. Much research has focused on the effect of trauma on neutrophil's individual capacities to kill bacteria with conflicting interpretations as a result. For adequate determination of the neutrophil's capacity to eradicate bacteria from tissue of trauma patients we developed novel in-vitro assays in which neutrophils are tested for all of these functions combined. This assay allows us to identify dysfunctional neutrophils adequately. The main focus of this study is the determination of the functionality of aberrant neutrophils circulating in the peripheral blood of severly injured following trauma.
Phase 3 multicenter study to be conducted in up to 90 qualified participating sites globally to assess the efficacy and safety of Reltecimod vs placebo in patients with sepsis-associated Stage 2/3 AKI.
The global burden of sepsis is substantial with an estimated 15 to 19 million cases per year; the vast majority of these cases occur in low income countries. New therapeutic approaches to sepsis are desperately required; considering the global burden of sepsis these interventions should be effective, cheap, safe and readily available. The aim is to study the synergistic effect of vitamin C, hydrocortisone and thiamine on survival in patients with severe sepsis and septic shock.
Severe sepsis leads a high morbidity and mortality by causing organ damage at distance. The treatment relies on early antibiotic therapy and hemodynamic resuscitation. Hypothesis: high flow nasal cannula (HFNC) could reduce work of breathing and improve the outcome of patients with severe sepsis and peripheral perfusion. Objective: the aim of this study is to evaluate the efficacy of HFNC for improving sixty-day survival in patients with severe sepsis. Design: multicenter parallel-group randomized clinical trial. Method: 592 adult patients with a diagnosis of severe sepsis in the first 12 hours of admission in the Emergency Room will be randomly assigned to an experimental or control group. In the experimental group, HFNC will be administered until the resolution of sepsis or until required mechanical ventilation, either invasive or non-invasive. In the Control group, conventional oxygen will be administered, if required. Sixty-day survival will be the primary outcome. The study is powered to demonstrate an improvement in survival from 70% in control group up to 80% in the HFNC group. The secondary outcomes will be reducing the need for vital support (mechanical ventilation, dialysis, vasoactive drugs) and physiological (acidosis, clearance of lactate, SvO2 and SOFA). Statistical analysis: Kaplan-Meier curves and Cox proportional hazard models will be calculated for all-cause sixty-day survival. If the results are conclusive, they will have immediate application in medical practice.