Pharmacokinetics and Safety of TIN816 in Patients With Sepsis-associated Acute Kidney Injury
Acute Kidney Injury Due to SepsisThe purpose of this study is to characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile and to evaluate the safety and tolerability of TIN816 in hospitalized adult participants in an intensive care setting with a diagnosis of sepsis-associated acute kidney injury (SA-AKI).
Comparison Between HA330 Hemoperfusion Filter Hemodialysis and Conventional High-Flux Hemodialysis...
Renal DysfunctionSepsis1 moreThe purpose of this study is to compare the effectiveness between conventional hemodialysis and hemodialysis using hemoperfusion adsorbents in renal dysfunction caused by sepsis
Effect of Heart Rate Control With Ivabradine on Hemodynamic in Patients With Sepsis
SepsisIvabradine2 moreSepsis, a life-threatening syndrome, is often accompanied by tachycardia in spite of adequate volume resuscitation to correct hypovolemia and vasopressor medication to correct hypotension. Recently, relevant studies have shown that sustained tachycardia in sepsis was also related to high mortality, and appropriate control of heart rate could improve prognosis. Ivabradine reduces heart rate directly without a negative inotropic effect through inhibition of the If ionic current,which is absent from the traditional rate control drug (beta-blockers). This is a prospective, multicenter, randomized, open label study designed to compare ivabradine with placebo on the difference of heart rate and haemodynamics in patients with sepsis.
Microcirculation Properties of Albumin for Fluid Resuscitation in Septic Shock
SepsisSevere2 moreThe sublingual microcirculation is impaired in sepsis and septic shock. Sidestream dark field imaging technology has been developed into a clinical tool to help the clinician assess the microcirculation at the bedside. The ideal resuscitation fluid has not been identified. The investigators aim to use this new bedside technology to establish the microcirculation properties of two popular resuscitation fluids.
RCT Cefiderocol vs BAT for Treatment of Gram Negative BSI
Bloodstream InfectionsThe purpose of this study is to determine whether a new antibiotic, Cefiderocol which works against a wide variety of gram negative bacteria, is equally effective as the antibiotics that are currently used as current standard of care.
Bacteremia From Periodontal Treatment to Elucidate the Underpinnings of Sepsis
BacteremiaPeriodontal Diseases2 moreApproximately 40,000 Swedes suffer from sepsiseach year, about 20% die. Biomarkers that are sensitive to current or previous bacteremia are needed in the treatment of sepsis. Bacteremia from periodontal treatment is predictive and occurs in 13-75%. The study's hypothesis is to utilize bacteremia from periodontal treatment to evaluate biological markers for current or previous bacteremia. A. What are the long term clinical, and 'omics related CVD-phenotypical effects from treating periodontal disease compared to an untreated group? B. Can biomarkers be used for detecting a bacteremia or previous bacteremia? C. Are the effects from bacteremia on cardiovascular biomarkers related to the individual's antimicrobial peptide profile? D. Does the presence of bacterial proteases, such as gingipain, relate to having a bacteremia from periodontal treatment and the systemic response from a bacteremia? Significance: The project has the potential to shorten the time to treat sepsis, which in turn shortens hospital stay and higher survival. The possible definition of protective AMP-profile could translate to future pharmacologic intervention and improve the treatment of sepsis as well as prophylactic treatment at dental treatments.
Early Empiric Anti-Mycobacterium Tuberculosis Therapy for Sepsis in Sub-Saharan Africa
TuberculosisHIV I Infection1 moreIn sub-Saharan Africa, tuberculosis (TB) is the etiology of 25-50% of bloodstream infections (BSIs) and the leading cause of sepsis among people living with HIV. TB BSI is associated with 20-50% mortality, and 20-25% of deaths occur within five days of admission. TB BSI is difficult to identify clinically and microbiologically. Given that the high prevalence of TB BSI is under-recognized, most patients with sepsis in sub-Saharan Africa do not receive early anti-TB therapy. The hypothesis of this study is that immediate and optimally dosed anti-TB therapy will improve 28 day mortality in patients with sepsis in Uganda and Tanzania. Therefore, the overall goal is to conduct a phase 3 multi-site open label 2x2 factorial clinical trial of 1) empiric immediate initiation of anti-TB therapy plus standard care compared to diagnosis dependent anti-TB therapy plus standard care and 2) sepsis-specific dose anti-TB therapy plus standard care compared to conventional WHO weight-based dose anti-TB therapy plus standard care for the treatment of sepsis in people living with HIV admitted to our longstanding collaborative research sites at either the Mbarara Regional Referral Hospital in Mbarara, Uganda, or Kilimanjaro region hospitals in Moshi, Tanzania.
Epirubicin for the Treatment of Sepsis & Septic Shock
SepsisThe study will assess the safety of low doses of epirubicin in sepsis patients. Therefore the study will look for side effects in patients treated with low dose epirubicin compared to control patients. In animals, low dose epirubicin has been shown to induce tolerance to infection and increase survival in septic mice. The study will also look for positive effects on organ function in humans. The investigators hypothesize that low-dose epirubicin can be used therapeutically to improve the disease course and lessen mortality of patients with sepsis. In a first step, the investigators aim at proving that low-dose epirubicin can safely be administered to sepsis patients and will perform a dose-escalation multi-center trial.
Immunoinflammatory Regulation of Esketamine in Septic Patients
EsketamineSepsis2 moreStudies have shown that excessive systemic inflammatory response and concomitant immunosuppression are the main cause of early death in patients with sepsis. Therefore, it is very important to reduce excessive inflammation and improve immunosuppression in the acute phase of sepsis. Clinical studies have shown that esketamine combined with propofol for sedation has been proven to be safe and effective for septic patients in the ICU due to its cardiovascular stability. Previous studies have demonstrated that esketamine has anti-inflammatory effects against depression and surgical stress. Our preliminary experimental studies have found that esketamine had strong anti-inflammatory effects in the acute phase of sepsis. However, it is not clear whether esketamine could reduce excessive inflammation and improve immunosuppression in septic patients primarily sedated with a continuous infusion of propofol. This intervention study is to investigate whether three consecutive days of intravenous esketamine infusions via infusion pump (0.07 mg/kg/h) could reduce excessive inflammation and improve immunosuppression in septic patients requiring mechanical ventilation in the ICU under sedation primarily with propofol.
Unfractioned Heparin for Treatment of Sepsis Caused by Abdominal Infection
SepsisGram-Negative Bacterial Infections1 moreSepsis is the leading cause of death in intensive care units and a major public health concern in the world. Heparin, a widely used anticoagulant medicine to prevent or treat thrombotic disorders, has been demonstrated to prevent organ damage and lethality in experimental sepsis models. However, the efficacy of heparin in the treatment of clinical sepsis is not consistent. Caspase-11, a cytosolic receptor of LPS, triggers lethal immune responses in sepsis. Recently, we have revealed that heparin prevents cytosolic delivery of LPS and caspase-11 activation in sepsis through inhibiting the heparanase-mediated glycocalyx degradation and the HMGB1- LPS interaction, which is independent of its anticoagulant properties. In our study, it is found that heparin treatment could prevent lethal responses in endotoxemia or Gram-negative sepsis, while caspase-11 deficiency or heparin treatment failed to confer protection against sepsis caused by Staphylococcus aureus, a type of Gram-positive bacterium. It is probably that other pathogens such as Gram-positive bacteria might cause death through mechanisms distinct from that of Gram-negative bacteria. Peptidoglycan, a cell-wall component of Gram-positive bacteria, can cause DIC and impair survival in primates by activating both extrinsic and intrinsic coagulation pathways, which might not be targeted by heparin. We speculate that the discrepancy between the previous clinical trials of heparin might be due to the difference in infected pathogens. Thus, stratification of patients based on the type of invading pathogens might improve the therapeutic efficiency of heparin in sepsis, and this merits future investigations.