Active clinical trials for "Shock, Septic"

Persistent tachycardia in sepsis or multi-organ dysfunction syndrome (MODS) is an ominous sign. This usually comes under control with judicious use of antibiotics, fluid resuscitation, sedation. Uncontrolled tachycardia in systemic inflammatory response syndrome and sepsis deprives the heart muscle of oxygen. As it progresses, insufficient heart muscle nutrition eventually leads to myocardial dysfunction. It can also present as heart failure. In acute coronary syndromes, beta blockers are used to control heart rate. However in MODS, it cannot be used due to hemodynamic instability and worsened myocardial function. Sinoatrial (SA) myocytes are the pacemaker cells in the heart. Pacemaker activity involves several ionic currents that influences spontaneous depolarization of SA node including I(f) current. The word I(f) means funny, because this current has unusual properties as compared with other currents known at the time of its discovery. It is one of the most important ionic current for regulating pacemaker activity in SA node. Ivabradine is an I(f) current inhibitor in SA node. Currently, it is the only agent shown to clinically lower heart rate with no negative inotropism or effects on conduction and contractility.so usage of Ivabradine to control tachycardia in patients with septic shock may help to improve myocardial filling and cardiac output. Marcos L.Miranda et al. found that Ivabradine was effective in reducing microvascular derangements evoked by experimental sepsis, which was accompanied by less organ dysfunction. These results suggest that ivabradine yields beneficial effects on the microcirculation of septic animals. No data found on effect of Ivabradine on the microcirculation of human. In this study the investigators will investigate the effect of Ivabradine on perfusion in capillary circulation using Cytocam video microscope, Braedius®.

Toxic Shock Syndrome (TSS) a severe condition with high morbidity and mortality results from the hosts overwhelming inflammatory response and cytokine storm. Staphylococcal superantigen toxins are the main causative agents. Toxic shock syndrome toxin (TSST-1) being responsible for almost all of menstruation associated and more than 50% of all other cases. There is no specific therapy. The aim of this study is to demonstrate the safety and tolerability of the BioMed recombinant toxic shock syndrome toxin (rTSST-1) Variant Vaccine in healthy adults. The second aim of the study is to measure antibodies in the blood of these healthy volunteers which have been produced in response to treatment with the BioMed rTSST-1 Variant Vaccine. These antibodies are expected to be important in resistance against the diseases. 46 healthy adults, male and female, age 18-64 years will be assigned to 6 dose groups of the vaccine at the Department of Clinical Pharmacology of the Medical University of Vienna. The patients will be monitored for vital signs, hematology, clinical chemistry, blood cytokine level and antibodies against TSST-1. Immunization will be repeated 4 weeks after the first with the same dose.

The trial enrolls patients with early severe sepsis or septic shock displaying at least one newly developed organ dysfunction and showing clinical evidence of pulmonary or abdominal infection. The primary goal of the trial is to assess the pharmacokinetics and pharmacodynamics of the new monoclonal antibody CaCP29 and to characterize safety and tolerability as well as evaluate parameters of efficacy.

Sepsis is one of the most frequent reasons for referral to emergency departments (EDs) worldwide. The incidence of sepsis is likely to rise in the upcoming years. Sepsis has a tendency to become more serious when left untreated with a high mortality rate, exceeding even those of myocardial infarction and stroke. Therefore, much effort has been put in to start with appropriate therapy as early as possible. Early goal-directed therapy (EGDT) in the emergency department with fluid resuscitation, administration of vasopressors/vasodilators and intravenous antibiotics in patients with severe sepsis and septic shock has indeed decreased mortality substantially. Emergency medical services (EMS) personnel have already made a significant difference in improving care for patients with acute coronary syndrome, multiple trauma and stroke. Patients with severe sepsis or septic shock could also benefit greatly from timely pre-hospital care. Earlier recognition and initiation of treatment by EMS personnel may improve survival even more. Interestingly, the first hour of ED presentation seems to be the most critical hour. Administration of antibiotics and fluid resuscitation in the pre-hospital setting will reduce the time to administration substantially. In adults, to the best of our knowledge, no studies on the effect of pre-hospital administration of antibiotics have been performed. In children with meningitis, some uncontrolled studies show contradictory results, most probably due to bias by severity. We propose a non-blinded randomised multicentre clinical trial study on the efficacy of early, pre-hospital intravenous administration of broad spectrum antibiotics (ceftriaxone), which are effective against a wide variety of infectious pathogens that cause most common community-acquired infections) in patients referred to the ED with suspected severe sepsis or septic shock. Objective: To evaluate whether early, pre-hospital administration of antibiotics, together with training of ambulance personnel in recognizing and initiating treatment reduces 28-day mortality in patients referred to the ED with suspected severe sepsis or septic shock Study design: Non-blinded randomized multicentre clinical trial nested within a stepped wedge design Study population: All patients above the age of 18 years, with suspected severe sepsis or septic shock and transferred to the ED by ambulance, are eligible for study inclusion Intervention: prehospital antibiotics (ceftriaxone 2000 mg intravenously) Main study parameters/endpoints: 28-day mortality, hospital length of stay, admission to intensive or medium care unit (ICU/MC), time to administration of antibiotics. Follow up of one year. QoL after one month after discharge.

Assess the effect of fluids and norepinephrine for mean arterial pressure titration to patients' usual level on the microcirculation of initial resuscitated hypertensive septic shock patients.

Life-threatening infections account for 10% of all intensive care unit admissions and constitute the second more frequent cause of death in the ICU after heart diseases. The most common cause of death in patients admitted with life-threatening infections is multi-organ failure that is mediated by severe inflammation. Given the relationship between inflammation and blood clotting, blood-thinners (also called anticoagulants) have been used to decrease inflammation and the formation of small clots. Several lines of evidence suggest that heparin, a proven and inexpensive blood-thinner, may reduce improve survival in patients diagnosed with life-threatening infection. The primary objective of this study is to demonstrate the feasibility of enrolling patients in a large randomized controlled trial investigating heparin in patients with severe infections. In this study, patients with life-threatening infections will have an equal chance of receiving an intravenous infusion of heparin, or a low dose of a similar drug to prevent of blood clots while patients are immobile. The primary purpose of the study is to demonstrate that an average of 2 patients per site, per month, can be enrolled. Other measures of feasibility include the consent rate, the number of protocol violations that occur during the trial, and the number of dose reductions needed due to excessive anticoagulation. To study the biologic effects of heparin in patients with severe infection, specific laboratory markers will be measured and analyzed. If the feasibility of the trial is confirmed, a large randomized trial designed to tell if heparin can safely improve survival will be conducted. Given its low cost and availability, if heparin is shown to improve survival in patients with severe infection, adoption of this therapy on a global scale is anticipated.

The Patient evaluated in Emergency room since admission and detailed history and clinical examination done .The in hospital cases where sepsis is the culprit and shifted to Intensive Care Unit (ICU) in view of septic shock were included since onset of shock. Initial fluid resuscitation done and if the patient were no fluid responsive they were randomized into arms noradrenaline or terlipressin and the dose escalated to achieve the primary objectives. At the same time the strict vitals monitoring and standard medical therapy for sepsis including antibiotics and other supportive therapy continued. The patients were followed up till discharge, death or up to 28days after enrollment into the protocol (whichever the longest). The detail methodology has been explained in column 14 later.

Sepsis has been characterised as a dysregulated host response to infection. Adjunctive therapies targeting the inflammatory cascade are being increasingly explored, although to date, have failed to demonstrate consistent benefit, and sepsis continues to manifest poor outcomes. Hospital mortality in patients with septic shock remains as high as 22% in Australia and New Zealand. From a global perspective, 31 million sepsis and 19 million severe sepsis cases are expected to be treated in hospitals all over the world per year. To date, experimental data have reported that both high dose intravenous vitamin C and corticosteroids attenuate the acceleration of the inflammatory cascade and possibly reduce the endothelial injury characteristic of sepsis, enhance the release of endogenous catecholamines and improve vasopressor responsiveness. Therefore, the investigators plan to conduct a feasibility pilot prospective, multi-centre, randomised, open-label, trial in ICU patients with septic shock to test whether the intravenous administration of high dose Vitamin C (6g/d), Thiamine (400mg/d) and Hydrocortisone (200mg/d) leads to a more rapid resolution shock and vasopressor dependence.

The aim of this study is to evaluate the efficacy of early metabolic resuscitation with combination therapy using vitamin C and thiamine in improving organ function and survival in patients with septic shock.

Septic shock is a highly lethal condition associated with a mortality risk of 30 to 60%. Optimizing tissue perfusion and oxygenation is the aim to decrease mortality and morbidity in septic shock patients. Persistent hyperlactatemia after initial resuscitation is particularly difficult to interpret, although optimizing systemic blood flow might reverse ongoing hypoperfusion. Nevertheless, if persistent hyperlactatemia is caused by non-hypoperfusion-related mechanisms, then sustained efforts aimed at increasing cardiac output (CO) could lead to detrimental effects of excessive fluids or inotropes. Another potential alternative resuscitation target is peripheral perfusion as assessed by capillary refill time (CRT), mottling score or central-to-toe temperature differences. Reversal of abnormal peripheral perfusion might represent improvement in tissue hypoperfusion with the advantage of a faster recovery than lactate. Hypothesis: Peripheral perfusion guided resuscitation in septic shock is associated with lower mortality, less organ dysfunctions, less mechanical ventilation (MV), less vasopressor load, and less renal replacement therapies than a lactate-targeted resuscitation strategy. Main Objective To test if peripheral perfusion targeted resuscitation in septic shock is associated with lower 28-day mortality than a lactate targeted resuscitation. Design: Multicenter, Parallel Assignment randomized controlled study, conducted under supervision of an independent Data Safety Monitoring Board (DSMB). Interventions: Active Comparator- Peripheral Perfusion guided resuscitation Active Comparator- Lactate guided resuscitation Randomization: 1:1 the randomization using a block size of eight will be stratified according to participating centers. Trial size: 400 randomized patients in 30 ICUs.