Clinical Research Directory

Dynamic SvO2 in Predicting Fluid Responsiveness in Septic Shock

This prospective observational diagnostic accuracy study investigates the efficacy of dynamic central venous oxygen saturation in predicting fluid responsiveness in septic shock, compared to measurements obtained using echocardiography (VTI) and cardiometry. We will correlate the changes in measuring cardiac output by both echocardiography and cardiometry with the changes in dynamic central venous oxygen saturation both at baseline and after fluid challenge to investigate the efficacy of dynamic central venous oxygen saturation in predicting fluid responsiveness in septic shock.

Adjunctive Fludrocortisone in Septic Shock

Sepsis is a life-threatening condition caused by the body's dysregulated response to an infection. While corticosteroids are known to help stabilize blood pressure in septic shock, their ability to reduce mortality is still debated. Recent analyses suggest that combining fludrocortisone with hydrocortisone may be more effective at saving lives than hydrocortisone alone. To test this hypothesis, a large, definitive international trial is needed. However, this research proposal is for a smaller pilot study (Phase II) involving 32 critically ill patients. The primary goal of this pilot is to determine the feasibility of conducting the subsequent large-scale trial that would compare hydrocortisone alone against the combination therapy and potentially change medical practice.

Written Sepsis Education for Patients

This pilot feasibility randomized controlled trial (RCT) aims to determine if it feasible to recruit, deliver, and evaluate a written discharge educational material (a brochure) to adult Intensive Care Unit (ICU) patients diagnosed with sepsis. The main questions it aims to answer are: 1. Feasibility to identify and enroll \>80% of eligible participants 2. Feasibility to recruit 30 participants over a 6-month period 3. Fidelity of intervention, assessed as \>75% of participants receiving assigned intervention Researchers will assess the feasibility of comparing two groups: (1) Control - usual ICU discharge care, and (2) Intervention - usual ICU discharge care plus the receipt of an educational sepsis brochure and an explicit opportunity to ask questions about sepsis, answered by a trained intensive care unit (ICU) Registered Nurse. Participants will receive intervention or control just prior to their discharge from ICU. They will complete online or phone survey assessments 24-48 hours post ICU discharge and 15-days post hospital discharge. Mortality and readmission data will additionally be assessed at 30-days post-discharge.

Hemodynamic Venous Congestion Ultrasound (VExUS) by ICU Nurses in Sepsis Patients.

Sepsis is a serious condition where the body's immune response to infection overreacts, leading to organ damage and death. Venous congestion, a buildup of blood in the veins, can occur in sepsis and contribute to organ injury. VExUS (Venous Excess Ultrasound Score) is an ultrasound method that can detect congestion early. This study examines whether ICU nurses, after training, can perform VExUS reliably, explores their experiences, and investigates links between VExUS findings and clinical outcomes.

Role of Transposable Elements in Septic Immune Aging

The goal of this observational study is to learn about how transposable element levels affect the patient outcomes in sepsis. The main questions it aims to answer is: 1. Do transposable elements prematurely age the immune systems of patients with sepsis? 2. Do transposable elements correlate with increased mortality in patients with sepsis in the ICU? 3. Do transposable elements correlate with increased amount of secondary infections in patients with sepsis in the ICU? Participants will have blood drawn from them but will not be subjected to additional interventions.

Eduction in ImmunoSuppressive Regimen Among Kidney Transplant Recipients Patients Admitted to the Intensive Care Unit for Septic Shock and/or Acute Respiratory Failure

Kidney transplantation is the treatment of choice for end-stage chronic kidney disease. Kidney transplantation is at the first rank of solid organ transplantation in France, with 3,376 grafts performed in 2022. Immunosuppressive therapy, required to prevent graft rejection, exposes graft recipients to complications related to decreased immunity, including opportunistic infections and neoplastic complications. After the earlt post-transplantation period, up to 10% of kidney transplant recipients will require admission to the intensive care unit (ICU). The main reasons for admission are septic shock and acute hypoxemic respiratory failure. ICU stay has a significant impact on these patients with a mortality rate reaching 40%, that remains increased even after ICU discharge. Furthermore, an impact on graft function has been demonstrated, with deterioration of graft function in 1/3 of patients, and among those, up to one in two will require resumption of renal replacement therapy (RRT). Although the occurrence of septic shock or acute respiratory failure related to an infection is more common and severe, the optimal management strategy for immunosuppressors is not defined in kidney transplant recipients admitted to the ICU in those settings. Maintain a high level of immunosuppressive therapies may hinder the recovery from the acute critical condition. Furthermore, these treatments have a narrow therapeutic index; for instance, the management of calcineurin inhibitors is challenging in the ICU due to pharmacodynamic changes associated with the acute situation (distribution volume, organ failure) and the numerous potential drug interactions that carry inherent risks of overdose. the investigators hypothesize that a reduction in the level of immunosuppressive treatments could promote recovery in kidney transplant recipients admitted to the ICU for septic shock and/or acute hypoxemic respiratory failure, without adversely affecting the risk of rejection or long-term renal prognosis.

A Combination Therapy With Ceftazidime and Fosfomycin Will be Compared to Ceftazidime Alone in Hospitalized Adult Patients With Suspected Severe Gram-negative Bacterial Infections

The goal of this clinical trial is to : 1. Test whether the combination of CAZ±AVI and FOS leads to superior clinical outcomes in patients with severe suspected Gram-negative bacterial infection, as demonstrated by a shorter time to normalization of quick Sequential Organ Failure Assessment (qSOFA) parameters and reduction in C-reactive protein (CRP) compared to standard of care (CAZ±AVI alone) 2. to further characterize the safety profile of this combination therapy In the presence of such an infection, standard treatment is to start intravenous antibiotic therapy. Ceftazidime (Fortam®), or ceftazidime-avibactam (Zavicefta®), is a standard antibiotic commonly used for this purpose (for very resistant bacteria, the compound avibactam is included to protect ceftazidime from being broken down by bacteria). Researchers will compare ceftazidime (or ceftazdime-avibactam) plus fosfomycin versus ceftazidime alone with placebo (i.e. a look-alike substance given with no drug) to examine whether the addition of another intravenous antibiotic, fosfomycin, would lead to faster recovery from severe infection and evaluate the tolerability of this combination. Participants will: * Be randomly assigned to either the intervention group or the control group. * The intervention group will receive ceftazidime (with avibactam if multidrug resistant bacteria are suspected, per routine practice) and intravenous fosfomycin, and the control group will receive ceftazidime (with avibactam if multidrug resistant bacteria are suspected) and placebo. * Either treatment will be given for 3 days, three times daily (or less frequently, depending on renal function). * Provide a few extra blood samples (for CRP measurement, a protein marker of inflammation) during the first few days of the study. * Be contacted in the hospital or by phone if discharged on day 28 to be asked a few questions.

Study on the Construction and Application of Early Warning Model of Sepsis in Critically Ill Patients

The condition of sepsis patients changes rapidly, whom are often accompanied by impaired respiratory, circulatory, renal, and coagulation functions. So far, the prognosis of sepsis at home and abroad is not ideal. Participants was randomly included in this research project on the pathogenesis and prevention of sepsis due to typical sepsis symptoms. the investigators will collect appropriate clinical specimens for analysis of immune cell functions and pathogenic microorganisms combined with individual patient research. This study will enable sepsis patients to be identified early and receive earlier anti-sepsis treatment, which is expected to improve the prognosis of sepsis, shorten hospitalization time, and reduce treatment costs. The above-mentioned tests and analyses do not increase the economic burden on the participants, and the required expenses are all paid from the project funds; they do not affect the prognosis and rehabilitation process of participants, and do not have adverse effects on the health of participants.

Fibrinolysis Resistance in Infection and Trauma

Blood coagulation disorders are often seen in critically ill patients e.g. with severe infection or following extensive injury, that can lead to life threatening events as a result of excessive blood clot formation leading to organ failure. This study aims to use Viscoelastic Testing (VET) technology to detect patients at risk of excessive blood blot formation at the bedside, test new blood coagulation drugs, and guide life-saving use of blood modifying treatments.

Proteinuria During Sepsis and Septic Shock: Characterization and Association With ARDS

ARDS is a pulmonary edema injury. Among its etiologies, it can be secondary to septic shock. Managing septic shock involves hemodynamic optimization with significant fluid and sodium inputs. Fluid and sodium inputs in ARDS worsen respiratory failure through capillary leakage, and a restrictive input strategy is clinically beneficial (reduced mechanical ventilation duration and ICU stay). Predicting ARDS onset in septic shock allows for optimized fluid and sodium input management, adopting a restrictive rather than liberal approach to minimize deterioration in respiratory function.