Clinical Research Directory

Plasma Exchange in Children With Severe Sepsis and Septic Shock

The aim of the study will be to to evaluate whether therapeutic plasma exchange (TPE) reduces mortality in critically ill children with severe sepsis or septic shock compared to the standard care of sepsis alone. The study population will be divided into two groups, the first group will receive standard sepsis management plus therapeutic plasma exchange and the second one will receive the standard sepsis management alone . Then we will assess the effect of TPE on : Severity of organ dysfunction (pSOFA score) , duration of vasopressor support , length of PICU stay, time to hemodynamic stabilization , and on inflammatory and coagulation biomarkers

Clinical Study on Monitoring the Plasma Concentration of Ceftazidime-Avibactam in Critically Ill Patients

This prospective observational study is conducted at the First Affiliated Hospital of Zhejiang University School of Medicine from June 1, 2021 to January 1, 2024. The study aims to characterize the population pharmacokinetics of ceftazidime (CAZ) and avibactam (AVI) in critically ill patients receiving ceftazidime-avibactam (CAZ-AVI), including patients with and without renal replacement therapy (RRT). Plasma concentrations of CAZ and AVI will be measured after the first-dose and steady-state administrations. Population pharmacokinetic and pharmacokinetic/pharmacodynamic target-attainment analyses will be performed to explore dosing strategies according to renal function and RRT status.

Descriptive Study of the Evolution in Proportion of Regulatory B Lymphocytes in Patients Hospitalized in Intensive Care for Severe Sepsis

Severe sepsis and septic shock are the most severe forms of sepsis (which associates a systemic inflammatory response with infection). These are serious pathologies with a lethality estimated at almost 40% at 28 days (after the onset of sepsis). After a first pro-inflammatory phase, a second compensatory phase called Compensatory Anti-Inflammatory Response Syndrome (CARS) takes place quickly. Patients then show signs of immunosuppression and profound alterations in immune functions. It is during this phase that the vast majority of deaths occur, far from the onset of the shock, which is related to the inability of the immune system to eliminate the initial infectious agent and / or a greater susceptibility Important to develop secondary infections (nosocomial infection, latent virus reactivation ...). The CARS phase has been the subject of studies focusing on measuring the plasma concentration of anti-inflammatory cytokines (such as Interleukin (IL) -10), the percentage of regulatory T lymphocytes (Treg), Or the percentage of monocytic expression of HLA-DR in septic patients. The investigator proposes to carry out the first study on a newly described regulatory lymphocytic subpopulation: regulatory B lymphocytes (Breg) from a quantitative and functional point of view in severe septic states.

Zinc Therapy in Critical Illness

Sepsis is a clinical syndrome often caused by a bloodstream infection that results in a common set of symptoms termed systemic inflammatory response syndrome (SIRS). Severe sepsis (sepsis with organ failure) is the leading cause of death in critically ill patients in the US. Most patients with severe sepsis need to be treated in the intensive care unit with mechanical ventilation and intravenous antibiotics. Between 30 to 50% of all severe sepsis patients die and quality of life in survivors is substantially reduced. New therapies are needed to improve clinical outcomes in patients with sepsis. A new area of interest in the treatment of critical illness is pharmaconutrition, in which micronutrients (like zinc) are studied and administered to determine if they affect the inflammatory response or immunologic processes in critical illness. The FDA does not regulate micronutrients and does not require rigorous pharmacokinetic (the study of how a drug or nutrient is metabolized in the body) testing so it is not clear how to dose micronutrients in critically ill patients. It is also not clear if critically ill patients would metabolize these micronutrients differently than healthy people and would need different dosing levels. This is true of zinc, the focus of this research study. Zinc is essential for normal immune function, oxidative stress response, and wound healing, and its homeostasis is tightly regulated. Zinc deficiency occurs in \>10% of Americans and leads to loss of innate and adaptive immunity and increased susceptibility to infections. The symptoms of zinc deficiency are similar to many of the symptoms of SIRS and there is strong biologic rationale to suggest that the zinc deficiency seen in nearly all sepsis patients may contribute to the development of sepsis syndrome and to the "immunoparalysis" common in sepsis patients This study has three specific aims, 1) to perform a phase I dose-finding study of intravenous zinc in mechanically ventilated patients with severe sepsis; 2) to define the pharmacokinetic of intravenous zinc in mechanically ventilated patients with severe sepsis compared to healthy controls; and 3) to investigate the impact of zinc on inflammation, immunity, and oxidant defense in patients with severe sepsis. A total of 40 critically ill patients from the FAHC intensive care units and 15 healthy controls will be enrolled in the study. The critically ill patient population will be divided into 4 dosing groups of 10 subjects (7 randomized to zinc and 3 to saline placebo). Group 1 will receive 500mcg/kg IBW/day elemental zinc in divided doses every 8 hours. If the 50th percentile of the normal plasma zinc range (110mcg/dL) has not been achieved in all patients by 7 days and there are no safety concerns, sequential groups of patients will receive increasing doses in 250mcg increments to the ceiling dose. Groups 2 through 4 will receive 750, 1000, and 1250mcg/kgIBW/day elemental zinc, respectively. Each participant will receive the intravenous zinc or placebo for a total of 7 days unless they die or leave the ICU earlier. Pharmacokinetic testing will be obtained from 40 of the critically ill subjects and in 15 healthy controls. Additional blood will be drawn during the infusion protocol to investigate the impact of zinc on inflammation, immunity, and oxidant defense.

GM-CSF to Decrease ICU Acquired Infections

The concept of acquired immunodeficiency after a first severe infection in the ICU is widely described in the literature. There is a dual risk: increased mortality and increased secondary infections. Several approaches of immunostimulatory treatments have been proposed in the literature. The treatment proposed by this study consists of the administration of Granulocyte-macrophage colony-stimulating factor (GM-CSF), colony stimulating factor widely used particularly in the USA where it is marketed. A phase 2 clinical trial was conducted in Germany in 2009. The main objective is to measure the incidence of ICU-acquired infections in 2 groups of patients treated by GM-CSF or placebo. ICU patients at risk are defined as surviving at D3 from a severe sepsis or septic shock and presenting a sepsis associated immunodepression. The detection of immunosuppressed patients will be achieved by measuring the HLA-DR (Human Leucocyte Antigen DR)with a threshold of less to 8000 sites. Our hypothesis is that the number of secondary infections (primary endpoint) will be significantly reduced in the treated group.

Monocyte Distribution Width (MDW) in the General Population of Emergency Department Patients With and Without Bacteremia

This project will evaluate the usefulness of Monocyte Distribution Width (MDW) for the diagnosis of blood culture positivity (BSI) in patients in the Emergency Department (ED) and reevaluate the usefulness of MDW in patients with BSI and sepsis. Consequently, if MDW indicate a high likelihood of bacteremia antibiotic management in patients with suspected bacterial infections will be changed and aid appropriate antibiotic administration.

De-escalation of Empirical Antimicrobial Therapy Study in Severe Sepsis

Rational: Severe sepsis is one of the leading cause of mortality in intensive care unit patients. Early initiation of an appropriate empirical antimicrobial therapy is associated with improved outcomes. In order to avoid an increase of selection pressure and the emergence of multidrug resistant pathogens, guidelines recommend to streamline the antimicrobial therapy after the identification of the pathogen responsible for infection. This strategy has been evaluated in several observational studies. However, at the bedside, few randomized clinical trials tested this strategy prospectively. Method: the investigators conduct a randomized clinical trial comparing a strategy based on de-escalation (streamlining of the empirical antimicrobial therapy) and a conservative strategy (continuation of the empirical antimicrobial therapy). The investigators first aim was to show that a strategy based on de-escalation is not inferior to a conservative strategy in terms of intensive care unit length of stay. Secondary aims are to compare the rate of mortality rate, the emergence of multidrug resistant pathogens, and the feasibility of de-escalation. The study is performed in nine intensive care units from four institutions, and 120 patients are required to validate the investigators hypothesis. New technologies for the rapid diagnosis of severe infections are investigated in an ancillary study.

A Multi-Center Data System and Collaborative Network in China for Severe Infection and Sepsis Children

1\. To research the current situation of severe infection in children in China, and to investigate the incidence, prognosis and disease burden of severe infection in children in different regions of China. 2. Establish the risk prediction model and diagnosi model of severe infection in children, and verify the accuracy of the model in multi-center; 3. To study the effectiveness and safety of different treatments in real diagnosis and treatment, and to evaluate the efficacy of subgroups under different ages and high risk factors.

Alveolar Dead Space as Predictor of Organ Failure in Severe Sepsis

This is an observational study to understand the changes in alveolar dead space in medical critically ill patients with severe infection (severe sepsis) requiring mechanical ventilation and the possibility to predict multi-organ failure. The measurement of alveolar dead space used to require sophisticated equipment and time. New ventilators have microprocessors that allow rapid mathematical calculation with minimal intervention.

Recovery From Acute Immune Failure in Septic Shock by Immune Cell Extracorporeal Therapy - Observational Long-term Outcome Follow up

Subjects previously enrolled / randomized in the ReActIF-ICE (Recovery from acute immune failure in septic shock by immune cell extracorporeal terapy - immune competence enhancement) study received either standard sepsis treatment (control group) or standard sepsis treatment and additionally the ARTICE treatment (treatment group) during their index hospitalization. All subjects are followed up for 90 days after enrollment. In this long term follow up study, the enrolled subjects shall be followed up beyond 90 days for up to 5 years.

Sepsis Clinical Decision Support [CDS] Master Enrollment Study Protocol

This protocol will collect real-world data retrospectively from the electronic health record (EHR) as data obtained from the delivery of routine medical care to develop a machine learning (ML)-based Clinical Decision Support (CDS) system for severe sepsis prediction and detection.