Clinical Research Directory

Comparative Efficacy and Safety of Propofol-Ketamine Combination Versus Propofol Monotherapy in Geriatric Patients Under Invasive Ventilation

The study is a prospective randomized controlled trial comparing the efficacy and safety of propofol-ketamine ("Ketofol") versus propofol monotherapy in geriatric ICU patients. Eligible participants are critically ill elderly patients with a history of cardiac disease who require endotracheal intubation and have not yet received sedation. The investigators focus on a specific population in which geriatric patients have different pharmacokinetics and pharmacodynamics and are more prone to side effects than other populations. Primary outcome: Incidence of hemodynamic instability (defined as hypotension requiring vasopressors), measured by mean arterial pressure (MAP) 5 minutes after induction Secondary outcomes include changes in blood pressure and heart rate, incidence of hypotension, vasopressor requirements, sedation depth, pain scores, cumulative sedative and opioid consumption, adverse events, ICU length of stay, and ICU mortality at predefined intervals.

Personalized Fluid Resuscitation in the Emergency Department: A Pilot Trial

The goal of this pilot clinical trial is to learn if a fluid assessment using non-invasive cardiac output monitoring (NICOM) is helpful for patients with sepsis who have low blood pressure in the Emergency Department (ED). The study will measure whether the NICOM assessment changes fluid resuscitation practices and is feasible in the ED setting. All patients will receive standard medical care. Patients assigned to the NICOM group will receive a one-time, non-invasive bedside fluid assessment using NICOM, in addition to standard care, and the results of the fluid assessment will be provided to the treating physician.

Safety and Efficacy of Polymyxin B Hemoperfusion (PMX) for Endotoxemic Septic Shock in a Randomized, Open-Label Study

Prospective, multicenter, randomized, open-label study of standard of care plus the PMX cartridge versus standard of care alone in patients with endotoxemic septic shock

The PvCO2-PaCO2/CaO2-CvO2 Ratio in Septic Shock

The ratio of the venous-arterial carbon dioxide partial pressure difference to the arteriovenous oxygen content difference (Pv-aCO₂/Ca-vO₂) may be a marker of anaerobic metabolism in patients with acute circulatory failure. This study aims to assess the prognostic value of the PvCO2-PaCO2/CaO2-CvO2 in the early phase of septic shock.

Core-to-Big-Toe Temperature Gradient as a Marker of Peripheral Perfusion in Adult Patients With Septic Shock

Septic shock is a life-threatening condition caused by severe infection that leads to dangerously low blood pressure and impaired blood flow to body tissues and organs. In the intensive care unit (ICU), restoring adequate tissue perfusion (blood flow) is essential during resuscitation. While doctors routinely monitor overall blood pressure, microcirculatory blood flow in peripheral tissues, such as the skin of the feet, can remain poor even after general blood pressure targets are reached. The difference between core body temperature and big-toe skin temperature (known as the core-to-big-toe temperature gradient, or ΔT) reflects blood vessel constriction in the extremities. When peripheral blood flow improves, skin temperature rises and this gradient narrows. This prospective observational study aims to evaluate whether serial measurements of the core-to-big-toe temperature gradient significantly change during the first 12 hours of ICU resuscitation in adult patients presenting with septic shock. The study also examines whether changes in this gradient correlate with standard indicators of clinical recovery, including blood pressure, vasopressor medicine requirements, and blood lactate clearance. All enrolled participants will receive standard, evidence-based medical care for septic shock in accordance with current international clinical guidelines; study participation will not interfere with, alter, or delay clinical treatment. Non-invasive measurements will be collected at three time points: at ICU admission (Hour 0), at 6 hours, and at 12 hours. These assessments include core body temperature, big-toe skin temperature measured with a calibrated infrared thermometer, finger capillary refill time, routine arterial blood pressure, and arterial blood lactate levels. If effective, this temperature gradient could provide clinicians with a simple, non-invasive, and cost-effective bedside indicator to monitor peripheral perfusion during critical care resuscitation.

Immune Dysregulation During Sepsis: A Natural History Cohort

Background: Sepsis is an illness that occurs when the body s immune system runs out of control. This can damage organs. Sepsis causes an estimated 1 in 5 deaths worldwide. In this natural history study, researchers want to learn more about how the immune system changes during sepsis. They hope this knowledge will help them find better ways to treat sepsis. Objective: To understand how sepsis affects the body over time. Eligibility People aged 18 years and older admitted to INOVA Fairfax Hospital in Virginia and who have sepsis. Design: Researchers will collect data from participants medical records. Participants will have blood drawn at least 5 times while they are in the hospital. Blood may be collected for up to 30 days, if they remain in the hospital that long. The blood will be taken from access lines that are already in place. Some blood draws will be optional. Participants may opt to have up to 3 tests of their heart function while they are in the hospital. Some participants may have a sample of fluid collected from their lungs. Participants will have a follow-up visit about 90 days after they join the study. This visit will be by phone call if they have left the hospital. They will fill out a questionnaire. They will answer questions about their health and how they feel. The call will last about 30 minutes.

Clinical Performance Study of Microbio InfectID-BSI for Detection of Bacteria and Yeast With Patient Blood Samples

The objective of the study is to determine the efficacy of the Microbio InfectID-BSI qPCR kit in a clinical laboratory environment using patient whole blood for pathogen detection and identification versus standard of care methods from blood culture. The objective of this study is to determine the sensitivity and specificity of the Microbio InfectID-BSI qPCR kit by the evaluation of clinical blood samples versus standard of care methods from blood culture.

Non-invasive Hemodynamic Optimization of Sepsis in Internal Medicine: a Randomized Study Comparing Therapy Guided by Non-invasive Hemodynamic Indices Versus Standard of Care.

Background and Rationale Sepsis affects 20 to 30 million people globally each year, with an estimated 48.9 million cases in 2017. Despite medical advances, it still carries a high risk of death. Since sepsis progresses rapidly, early treatment is essential. This includes not only starting antibiotics quickly but also managing fluid levels effectively. Research suggests that in sepsis, fluid problems are often due to poor distribution in the body rather than an actual lack of fluids. Currently, fluid and blood pressure management is often based only on monitoring arterial pressure, which may not provide a full picture of what's happening in the patient's circulatory system. More advanced indicators like Stroke Volume, Cardiac Output, and Peripheral Vascular Resistance can offer better guidance to optimize treatment and improve outcomes. New non-invasive devices such as NICaS (Non-Invasive Cardiac System) make it easier and faster to monitor these values. NICaS uses electrical impedance technology and is approved by both the FDA and CE. It is easy to use, does not require specialized training, and allows for a more personalized and accurate treatment approach by tracking key heart and circulation parameters in real time. Primary Objective The main goal of this study is to compare two treatment strategies for patients with sepsis admitted to medical wards, and see which one leads to better survival: * Fluid and/or vasopressor therapy guided by non-invasive hemodynamic monitoring (using NICaS), based on values like Stroke Volume, Cardiac Power Index, and Peripheral Vascular Resistance. * Standard fluid therapy based on the international Surviving Sepsis Campaign (SSC) guidelines. Secondary Objectives * Use of vasopressors: Check which strategy leads to less frequent use of vasopressor drugs and shorter treatment duration with them. * Kidney function: See which method is linked to fewer cases needing dialysis or kidney support. * Timing of vasopressors: Understand if giving vasopressors earlier leads to better short- and mid-term outcomes, such as lower death rates after 30 days, fewer ICU admissions, and shorter hospital stays. * Albumin levels and circulation: Track how blood albumin levels change with circulation status, to see if there's a link with fluid leakage (capillary leak) and risk of death. * Fluid balance: Analyze how fluid gains and losses relate to changes in heart and circulation measurements. * Microcirculation: Test if adding signs of small vessel (microcirculation) issues to the main heart and blood flow indicators improves predictions of how patients will do. * Prediction scores: Investigate whether combining NICaS readings with common scoring systems like SOFA or APACHE helps doctors predict patient outcomes more accurately. * Time to stability: Compare how quickly patients in each treatment group recover to a stable condition. According to Rosenthal and Kavic's criteria, a patient is considered stable when: -Their illness is improving -There's low risk of getting worse again - Organ support is stable - There's little chance of new problems arising - There are no major complications. Conclusion This study aims to evaluate whether a more personalized approach using real-time, non-invasive hemodynamic monitoring can lead to better outcomes in septic patients compared to standard care. If successful, this method could help reduce deaths, complications, and treatment costs in sepsis management.

Protocolized Reduction of Non-resuscitation Fluids Versus Usual Care in Septic Shock Patients

The objective of this trial is to assess the beneficial and harmful effects of a restrictive strategy for administration of non-resuscitation fluids in adult patients with septic shock.

Effect of Targeting Upper Normal Serum Magnesium Levels on Norepinephrine Requirements in Septic Shock Patients

The goal of this clinical trial is to assess the effect of targeting upper normal serum magnesium levels on norepinephrine requirements in adult patients with septic shock. The main questions it aims to answer are: 1. Does maintaining upper normal serum magnesium levels lower the total cumulative dose and duration of norepinephrine therapy? 2. Does this approach reduce the intensive care unit (ICU) length of stay, duration of mechanical ventilation and mortality? This study will compare an intervention group to a control group to see the effect of targeting upper normal serum magnesium levels. Participants will: * Have their serum magnesium levels assessed at baseline (Day 0), at three-day intervals (Days 3, 6, 9) thereafter and on the day of norepinephrine discontinuation. * Receive individualized intravenous magnesium sulfate infusions to achieve and maintain the target serum magnesium levels. * Have their demographic data collected and be monitored closely for clinical data, vital signs, Mean Arterial Pressure (MAP), urine output and laboratory parameters.

Evaluation of the Efficiency of Intermittent Enteral Nutrition on Multi-organ Failure From Patients With Mechanical Ventilation in Intensive Care Unit

This study aims to evaluate the efficiency of intermittent enteral nutrition versus continuous enteral nutrition to prevent from organ failures for patients at the acute phase of sepsis shock with mechanical ventilation in ICU.

Evaluation of the Clinical Frailty Scale (CFS) as a Risk Factor of Mortality in Adult Patients ≤65 Years of Age Admitted to Intensive Care for Septic Shock.

The aim of the study is to demonstrate that "frail" patients, defined as having a CFS score greater than or equal to 5, and "severely" frail patients, defined as having a CFS score between \[6-7\] as defined by Bagshaw et al (14), constitute an independent risk factor (RF) for mortality. In the same way, as an exploratory study, we will try to find out whether clinical frailty constitutes a risk factor for extending the length of hospital stay, the risk of short/medium-term readmission, as has already been demonstrated for patients admitted to intensive care from all causes (15), or for impaired quality of life. The objective is to have a better understanding of the implications and outcomes associated with pre-hospital frailty in young critically ill patients. This analysis will also help to clarify prognoses and contribute to better decision-making on the intensity and proportionality of care, as well as providing better information and helping to manage the expectations of patients and their families in terms of survival prognosis and subsequent quality of life.

Mechanistic Assessment of Norepinephrine Therapy vs. Angiotensin-II in Septic Shock

Despite best therapy efforts, sepsis and septic shock are associated with mortality rates of up to 40%. This clinical trial will determine the benefit of exogenous Angiotensin II versus norepinephrine (conventional care) treatment in septic shock patients. This trial will determine whether there are better predictors of septic shock severity. This approach may inform more appropriate treatment regimens and improve outcomes for these patients.

Myeloid Bias in the Bone Marrow of Septic Patients and Its Correlation With Disease Severity and Prognosis: A Single-Center, Prospective Cohort Study

Sepsis remains a leading cause of critical illness worldwide, yet the underlying mechanisms driving its profound and persistent immune dysfunction are incompletely understood. The bone marrow, as the birthplace of all immune cells, plays a central role in orchestrating systemic immune responses. Emerging evidence from animal models suggests that sepsis triggers emergency myeloid-biased hematopoiesis in the bone marrow, characterized by expansion of myeloid progenitors and myeloid-derived suppressor cells (MDSCs) at the expense of lymphoid and erythroid lineages. This bone marrow remodeling precedes peripheral immune alterations and may represent the initiating event of sepsis-induced immunosuppression. However, direct clinical evidence in humans is scarce. This prospective, single-center cohort study aims to systematically characterize bone marrow hematopoietic remodeling in patients with septic shock, compared to critically ill non-septic patients and healthy volunteers, and to determine whether the degree of myeloid lineage bias correlates with disease severity, immunosuppression, and adverse clinical outcomes. This study will enroll three cohorts. Bone marrow aspirates and peripheral blood samples will be collected at 48-72 hours post-enrollment for flow cytometric immunophenotyping of hematopoietic stem/progenitor cells, MDSC subsets, and PD-L1 expression, as well as cytokine profiling and exploratory single-cell transcriptomics. Rectal swabs will be collected synchronously for 16S rRNA sequencing and untargeted metabolomics to investigate the association between gut microbiota, microbial metabolites, and bone marrow myeloid skewing, testing the gut-bone marrow-immune axis hypothesis. Clinical severity (SOFA/APACHE II), secondary infections, and 90-day mortality will be assessed to evaluate prognostic value. By integrating bone marrow hematopoiesis, gut microbiome, and clinical outcomes, this study seeks to provide novel mechanistic insights into sepsis-induced immunoparalysis and identify potential biomarkers or therapeutic targets for immune restoration.

Serum Rennin Kinetics Versus Serum Lactate Kinetics as Predictors of Mortality in Septic Shock Patients

Whole blood lactate concentration is widely used in shock states to assess perfusion. We aimed to determine if the change in plasma renin concentration over time would be superior to the change in lactate concentration for predicting 28-day mortality in septic shock patients.

Prognostic Power of the VEXUS Score in Septic Shock: Effectiveness in Mortality Prediction

This study aims to evaluate the prognostic power of the VEXUS Score in predicting mortality among patients with septic shock in intensive care units.

Nucleosome Monitoring Relevance for Outcome Prediction in Critically Ill Patients

NUROPI is a single-centre, prospective, non-interventional study in the Intensive Care Unit (ICU) of Erasme Hospital (Hôpital Universitaire de Bruxelles, Brussels, Belgium). Some critically ill patients get worse during the first days of their ICU stay. Identifying them early could allow faster escalation of care. Nucleosomes are fragments of DNA wrapped around proteins called histones. They are released into the blood when cells die or when white blood cells form neutrophil extracellular traps (NETs). High blood levels of nucleosomes may reflect inflammation, clotting activation and organ damage. This study will measure the H3.1 nucleosome in the blood of 1,000 consecutive adult ICU patients. The measurement uses a CE-marked laboratory test (Nu.Q® NETs, chemiluminescence immunoassay on the IDS-i10 analyser). No additional blood sample is taken for the study. H3.1 is measured on the leftover plasma of blood samples already drawn for routine care, at ICU admission, 6 hours, day 1, day 3 and day 7. Patient treatment is not changed. Patients, or their relatives or legal representative, receive an information notice and may refuse participation at any time. The main question is whether H3.1, alone or combined with routine ICU data, can identify patients at high risk of clinical deterioration within 72 hours of ICU admission. Other questions concern the link between H3.1 and mortality, organ dysfunction, and ICU treatments, and how H3.1 levels change during the first week.

Fever Control Using External Cooling in Mechanically Ventilated Patients With Septic Shock

The best strategy for managing fever in patients with septic shock remains unknown. In a pilot study, the investigators showed that fever control at normothermia allowed a better control of shock and evolution of organ failures. In this second trial the investigators will conduct a multicentre, open-label, randomized controlled, superiority trial in which two strategies will be compared: 1. Respect of fever 2. Fever control at normothermia using external cooling The primary end point will be d-60 mortality.

Assessment of Microcirculatory Dysfunction in Septic Shock Patients by OCTA

Purpose and rationale: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis and septic shock are major public health problems killing one in every three patients. Microcirculatory dysfunction is frequent in septic shock. The duration and severity of this dysfunction have a prognostic impact by being associated with organ failure and mortality. Our study purposes to demonstrate the feasibility of optical coherence tomography angiography (OCTA) to improve assessment of microcirculatory dysfunction by showing that retinal and choroidal microcirculatory changes with prognostic impact are present during septic shock. Primary objective: To characterize the alterations of retinal and choroidal microcirculation in septic shock. We will test the hypothesis that retinal and/or choroidal microcirculation shows dysfunctional changes (lower vascular density, lower percentage of perfused small vessel, lower blood flow index and higher vascular heterogeneity) in septic shock patients. Secondary objective: To test the prognostic value of retinal and choroidal microcirculatory dysfunction in septic shock. We will test the hypothesis that higher magnitude and persistence of retinal and/or choroidal microcirculatory dysfunction beyond the successful macro-hemodynamic resuscitation are independent predictors of organ failure and mortality in septic shock patients. Study type: Two sequential observational studies. Study design: A cross-sectional case-control study followed by a prospective cohort study with a 90-days longitudinal follow-up period. Study population: 165 septic shock patients and 30 healthy controls. Study duration: 90 days from enrolment to final follow-up assessment. One to two years of enrolment.

Early Optimization of Ceftazidime Regimen in Critical Care

Hospital-acquired infections, most of which are caused by Gram-negative bacteria, are common in intensive care units and have a major impact on patient prognosis. Patient survival in severe sepsis and septic shock depends on the early administration of appropriate antibiotic therapy, with mortality increasing by 7.6% for each hour of delay, justifying the probabilistic use of broad-spectrum antibiotics such as ceftazidime, an essential betalactamine, particularly used for its activity against Pseudomonas aeruginosa, a frequent pathogen in nosocomial infections. It is currently recommended that ceftazidime should initially be administered as a 2g loading dose, followed by maintenance treatment by continuous infusion, at a dose adapted to renal function. The recommended dosage regimen, with its 2g loading dose, was developed using the median value of parameters from a pharmacokinetic model. This explains the findings of many critical care studies, which have found that 40-60% of patients initially have concentrations below target with the recommended dosing regimen. In the context of critical care, maintaining concentrations within the target therapeutic range is difficult due to variations in the elimination clearance of ceftazidime. Ceftazidime is mainly eliminated by the kidneys. Critical patients may have increased glomerular filtration rate, or, conversely, impaired renal function, with rapid variations in the event of severe infection. This leads to high intra- and inter-individual variability, and increases the risk of antibiotic under- or overdose when the maintenance dose is administered at a fixed dose (6g/d continuously). This high variability can also be observed in the volume of distribution (capillary leakage, oedema, perfusion volumes, effusions ...). In order to propose an individualised dosing regimen, we therefore propose an iterative randomised study to : * Step 1: FORTOPTIM\_1 Evaluation of an optimised dosage regimen based on literature data compared with the standard psological regimen. * Step 2: FORTOPTIM\_2 Build a pharmacokinetic model from the prospective data obtained in step 1. Based on this model, an individualised dosage regimen (loading dose and maintenance dose) will be obtained for step 3. * Step 3: FORTOPTIM\_3 Prospectively evaluate in a randomised trial the individualised dosing regimen previously defined (Step 2) by comparing it to the best dosing regimen determined in Step 1 or to the standard dosing regimen if there is no significant difference in Step 1.

Dynamic POCUS of Diaphragm Function to Predict Respiratory Failure in Septic Shock

This prospective observational cohort study aims to evaluate the prognostic value of serial bedside ultrasound assessment of diaphragmatic function in adult patients with septic shock. Diaphragmatic excursion, thickness, and thickening fraction will be assessed using point of care ultrasound at baseline and serially during the first 72 hours of intensive care admission. Dynamic changes in these parameters will be analyzed in relation to the development of respiratory failure, need for invasive mechanical ventilation, duration of mechanical ventilation, weaning and extubation outcomes, length of ICU stay, and mortality. The study will determine whether dynamic diaphragmatic ultrasound assessment can provide an early, non-invasive predictor of respiratory failure and adverse clinical outcomes in patients with septic shock.

Comparing Blood-Based Ratios for Predicting Outcomes in Sepsis and Septic Shock

Sepsis and septic shock are serious conditions associated with a high risk of organ dysfunction and death. Simple laboratory-based markers may help identify critically ill patients who are at greater risk of poor outcomes. This prospective observational cohort study compared the prognostic value of the neutrophil-to-lymphocyte ratio and the lactate-to-albumin ratio in adult patients with sepsis or septic shock admitted to the Surgical Intensive Care Unit at Benha University Hospital. A total of 60 participants were enrolled and followed for 28 days. The study evaluated the relationship of both laboratory ratios with 28-day mortality and compared their ability to predict mortality. Intensive care unit length of stay and progression of organ dysfunction were also assessed.

Microbiology Operations & Time Optimization in Sepsis

The goal of this study is to simulate turn-around times of blood cultures from blood culture collection to final communication of the result. The main objective is to develop a web-based tool that is able to simulate heterogeneous laboratory settings and to analyse the impact of infrastructure and opening hours on blood culture turn-around times.

Ionized Calcium as a Severity Marker in Septic Shock Patients

Sepsis is a serious condition where the body has an extreme, dysregulated response to an infection, often leading to life-threatening organ dysfunction. Low levels of ionized calcium (the active, free form of calcium in the blood) are common in critically ill patients admitted to intensive care units (ICUs). While established clinical scoring systems like the Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) help assess illness severity, there is a continuous need for rapid, cost-effective biological markers that can be measured immediately at the bedside using routine blood gas analyzers. The primary purpose of this observational study is to evaluate whether ionized calcium levels measured upon admission to the ICU can serve as an early marker of disease severity and outcome in adult patients diagnosed with sepsis or septic shock. Adult participants diagnosed with sepsis or septic shock who are admitted to the ICU will receive standard medical care. Routine arterial or venous blood samples will be analyzed at admission to measure ionized calcium and other standard laboratory markers. Researchers will correlate these calcium levels with baseline illness severity scores (SOFA and APACHE II) and evaluate patient outcomes, including 28-day mortality, length of ICU stay, and the need for mechanical ventilation or vasopressor medications.