Active clinical trials for "Sepsis"

Between 6 and 16% of patients presenting to hospital emergency departments have infections, with half of these having signs of systemic inflammation (known as 'sepsis'). A second issue is that, at time of presentation, it can be difficult to determine who has inflammation as a result of infection and who does not. Some of the patients with infections will deteriorate to organ failure ('severe sepsis') including failure of the heart and blood vessels to maintain normal blood pressure ('septic shock'). Septic shock as arguably the most dangerous form of severe sepsis is associated with a significant mortality, which can be reduced by early intervention. However identifying those patients who are at high risk of deteriorating to septic shock can be difficult on initial presentation to hospital, and thus these patients risk being 'triaged' to an inappropriate level of care and/or missing the crucial early interventions which can modify mortality. Equally failure to identify which patients have underlying infections can lead to potential inappropriate targeting of antibiotics. Existing clinical and laboratory tests are often unable to accurately identify those patients with infection, and those who are likely to deteriorate to severe sepsis and septic shock. Investigators in this group have recently identified several signatures of immune system activation which predict those patients who are likely to deteriorate, and which patients with suspected infection subsequently have this confirmed. Such tests would have major benefits for the management of patients with early suspected infection and sepsis if they can be translated into a test usable in everyday clinical practice. This study aims to determine the prevalence of these markers in a cohort of patients admitted with suspected sepsis, and their predictive ability for developing established septic shock. From this investigators aim to derive an optimal test, to be tested in a validation cohort (ExPRES-Sepsis II) which will be suitable for everyday clinical practice, and thus take the next step towards developing a market-ready test. Study hypothesis is: Measurement of markers of immune activation will allow i) Risk stratification for deterioration into severe sepsis ii) Risk stratification for death amongst patients presenting with sepsis iii) Identification of patients with confirmed sepsis

In this study, the investigators will dynamically detect the expression of an immune regulator- T cell Ig and mucin domain protein 3 (Tim-3) in patient with sepsis.

This is an observational study to identify the aetiology and factors associated with outcome of community-acquired sepsis and severe sepsis in Northeast Thailand. Potential study participants will be adult patients who are presented at the hospital with community-acquired sepsis. Clinical specimens (including blood, urine, sputum and throat swabs) will be collected from each participant on admission for culture, PCR and serological tests, and other laboratory tests, including inflammatory markers and genotyping. Participants' treatment will be closely monitored during the duration of their hospital stay. Blood will be again collected at 72 hours after admission. Participants will be contacted at 28 days after admission to determine clinical outcome by phone interview with standardized script. There will be a total of 5,020 patients enrolled in this study over 3 years.

Plasma midkine has reported to be elevated in infection and a regulator of angiotensin-converting enzyme (ACE). We aimed to investigate the plasma midkine in septic patients and its association with 28-day mortality and organ function, and also with plasma ACE and angiotensin II.

The aim of this prospective study is to assess the prognostic value of bioactive plasma adrenomedullin (ADM) in 600 patients with severe sepsis or septic shock in an international multicenter study and to validate the findings concerning the association of ADM concentration and the use of vasopressor therapy, organ failure and outcome.

The investigators hypothesize that doctors and nurses can undergo a brief period of training and then use ultrasound to accurately measure blood flow in a forearm artery after a brief period when this flow is interrupted with a blood pressure cuff, a measurement the investigators call reactive hyperemia. Reactive hyperemia indicates whether the small blood vessels in the body are healthy -- lower reactive hyperemia indicates worse small blood vessel function. When measured by experienced ultrasound experts, low reactive hyperemia strongly predicts death in critically ill patients with infection (severe sepsis). The investigators are conducting this study to determine if doctors and nurses, without specific pre-existing expertise in ultrasound, can be trained to make these measurements accurately. If so, the investigators will prove that these measurements can be applied reliably in real-world practice. The investigators also hypothesize that reactive hyperemia predict the outcomes of illness not just in patients with severe infection, but in other critically ill patients as well. Finally, the investigators hypothesize that reduced blood flow after blood pressure cuff occlusion is linked with other abnormalities of blood, previously identified in critically ill patients. For example, red blood cells from patients with severe sepsis have been shown to be stiffer than normal, so they are less able to flow along the small blood vessel passages of the body. Red blood cells become stiffer when there is a certain type of stress in the body known as "oxidative stress." If the investigators show that low reactive hyperemia, stiff red blood cells, and oxidative stress are linked, the investigators hope to develop new treatments that reduce oxidative stress, reduce the stiffness of red blood cells, and in turn improve reactive hyperemia. Improvements in reactive hyperemia indicate improvements in small blood vessel function. Better small blood vessel function means better delivery of oxygen throughout the body. The investigators believe that this will improve outcomes for critically ill patients.

Critically ill children have abnormal utilization of nutrients such as glucose, lipids and protein. Protein synthesis is increased mainly in the form of immune and signaling proteins, while synthesis of muscle and structural proteins is decreased. The metabolism of sulfur amino acids and specifically methionine and cysteine have not been investigated in critically ill septic children, despite that sulfur amino acids have important roles on thiol, antioxidant and epigenetic reactions, as well as precursor of glutathione (GSH). Methionine metabolism in critically ill children will be influenced by its rate of utilization through the transmethylation, remethylation and transsulfuration pathways, which are the major pathways of methionine metabolism. The investigators study aims to investigate the metabolism of methionine and cysteine in parenterally fed critically ill septic children. The investigators aim to determine the rates of transmethylation, remethylation, transsulfuration and GSH synthesis rates in critically ill septic children, to determine in vivo, whole body sulfur amino acid metabolism when sulfur amino acids are supplied by the parenteral route. The objective is to determine whether current parenteral intakes support GSH synthesis and if methionine metabolism differs when supplied by the parenteral versus the enteral route. Methionine parenteral requirements will be also studied by using the indicator amino acid oxidation and balance technique.

2 recent national reports 'Why Children Die' and 'Are we there yet?'identified deficiencies in recognising and managing sick children. Key recommendations from both reviews included the development and adoption of 'track and trigger' or a paediatric early warning score (PEWS) to better identify the sick or deteriorating child. PEWS tools offer the potential to identify and respond sooner to clinical deterioration. Capillary refill time (CRT) is a measure of skin blood flow and is a vital part of many early warning and resuscitation scores. It is a sensitive marker of infection and dehydration in children. However, due to how it is performed and interpreted CRT is prone to marked variability between observers. We have Medical Research Council (MRC) funding to develop an automated capillary refill device and user interface to provide a paediatric continuous early warning (PaedCEW) monitoring system. The PaedCEW system would complement and support current clinical practice and aim to address the difficulties of recognising ill children. We aim to recruit 20 ill children on the Paediatric Intensive Care Unit (PICU) with 2 matched controls without significant illness from the Nottingham Children's Hospital. The 20 ill children will have their CRT (and PaedCEW score) monitored before, during and after admission to PICU. This will allow correlation with invasive (BP, central venous oxygen saturations, lactate) and noninvasive (CRT, heart rate, cardiac output) measures of cardiovascular status during periods of stability and compromise. Matched controls will be monitored for around 24 hours. This pilot study will allow development of our system. This is a proof of concept study. This study aims to demonstrate a novel device for measuring CRT. Its correlation with noninvasive measures of cardiovascular status will enable a pragmatic comparison with current clinical practice. In addition, correlation with invasive measures of cardiovascular status will enable us to calculate sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV).

Molecules indicating endothelial injury may serve as biomarkers for severe sepsis because of the critical role of endothelial injury in organ dysfunction during severe sepsis. HSPA12B is primarily located in endothelial cells and detectable during sepsis. The investigators speculated that HSPA12B from endothelial cells might be correlated with severe sepsis.

Objective: to test the hypothesis that recombinant activated protein C (aPC) therapy improves the microcirculation of severe septic patients. Design: Prospective, open study. Setting: University 12-beds intensive care unit. Patients: Septic patients with at least two sepsis-induced organ failures occurring within 48 hours of the onset of sepsis were included in a one year period. Interventions: Patients who had no contraindication to aPC administration received aPC at a dose of 24 mcg/kg/h for 96 hours. Patients with contraindications to aPC infusion were considered as controls.