Clinical Research Directory

A Trial of Adjunctive Fludrocortisone (50mcg, 100mcg or Placebo) in Critically Ill Patients With Septic Shock Receiving Hydrocortisone, Evaluating Survival and Functional Recovery and the Influence of Transcriptomic Response

The FLUDRO-SHOCK trial is a large international randomised controlled double-blinded study aiming to improve treatment for people with septic shock, a life-threatening condition caused by severe infection. Patients with septic shock receive a steroid called hydrocortisone, but it is unclear whether adding another steroid, fludrocortisone, improves their chances of recovery and survival. This study will test two doses of fludrocortisone (50 mcg and 100 mcg) against a placebo to see which works best. It will also explore whether a person's unique immune response, based on their genes, affects how well the treatment works. The trial will involve up to 2,200 critically ill adults in intensive care units across Australia and other countries. Researchers will track survival, organ recovery, and quality of life for up to a year. The goal is to find the most effective and personalised way to use steroids in septic shock, potentially saving lives and improving long-term outcomes.

Serum GDF-15 and LGALS3BP as Prognostic Biomarkers in Sepsis

The purpose of this study is to find out whether blood levels of two proteins, GDF-15 and LGALS3BP, measured at intensive care unit admission and at 72 hours, can help predict survival and organ dysfunction in adult patients with sepsis or septic shock. Blood samples are collected together with routine laboratory tests, without additional needle sticks. The study does not change patient treatment.

Veno-arterial Carbon Dioxide Partial Pressure Difference (CO2gap) for Early Resuscitation of Septic Shock

Sepsis is a dysregulated host response to infection that leads to life-threatening organ dysfunction and represents a major healthcare problem. Septic shock is the most severe form, characterized by increased capillary permeability and vasodilation, resulting in hypotension and tissue hypoxia. Early identification and treatment of tissue hypoperfusion are pivotal components of initial resuscitation to limit progression to multiple organ dysfunction and death. The 2021 Surviving Sepsis Guidelines recommend guiding initial resuscitation by targeting decreases in serum lactate levels in patients with elevated lactate. However, although elevated lactate levels may reflect tissue hypoxia, serum lactate is not a direct marker of tissue perfusion. Hyperlactatemia may be attributable to mechanisms other than tissue hypoperfusion, such as accelerated aerobic glycolysis driven by excessive β-adrenergic stimulation or impaired clearance (e.g., in liver failure). The venous-to-arterial carbon dioxide partial pressure difference (CO₂ gap), which is inversely related to cardiac output, has been shown to reflect the adequacy of venous blood flow to remove CO₂ from tissues. The CO₂ gap is closely linked to microcirculatory blood flow during the early resuscitation phase of septic shock and may effectively identify persistent tissue hypoperfusion in shock states. A persistently high CO₂ gap during early resuscitation has been associated with significantly higher 28-day mortality and increased Sequential Organ Failure Assessment (SOFA) scores. Moreover, the CO₂ gap has been shown to respond to changes in cardiac output during inotrope infusion in patients with low blood flow, suggesting that its assessment could be useful for therapeutic adjustments. Therefore, there are compelling arguments to evaluate the usefulness of the CO₂ gap in guiding early resuscitation in patients with septic shock. The investigators postulated that CO₂ gap-guided early resuscitation may be more effective in improving outcomes than lactate-guided resuscitation.

Comparison of Cardiac Index Measurement Using Right Ventricular Pressure Curve Analysis and Thermodilution Via a Swan-Ganz IQ™ Catheter.

The pulmonary artery catheter (Swan-Ganz) is a standard tool in intensive care for measuring and monitoring cardiac index by thermodilution. The Swan-Ganz IQ™ model also allows continuous estimation of cardiac index through analysis of the right ventricular pressure wave, which could be useful for rapidly assessing changes in cardiac output during volume expansion response tests. However, the concordance between this continuous method and thermodilution remains poorly studied in real clinical conditions and may vary depending on certain clinical situations. This study therefore aims to compare the cardiac index measured by thermodilution with that estimated by right ventricular pressure waveform analysis based on data collected in clinical practice.

Systematic Adjunction of Vasopressine in Septic Shock

Septic shock is a syndrome associated with severe infection and a mortality rate of approximately 45%. In line with current recommendations, norepinephrine is the first-line vasopressor used in patients with septic shock. In a previous study, norepinephrine doses above 1 µg/kg/min were associated with mortality rates over 90%. In the same study, doses above 0.3 µg/kg/min were associated with a mortality rate of 40%. An increased mortality compared to the general 40% mortality of septic shock appears to be associated with norepinephrine doses as low as 0.3 µg/kg/min. Vasopressin stimulates V1 receptors, primarily located on vascular smooth muscle cells. When V1a receptors are stimulated, they induce vasoconstriction by activating protein kinase C via a Gq protein and various second messengers. Its use is validated in refractory shock states by international guidelines as a second-line vasopressor. This indication was further reinforced in the 2021 update of the septic shock management recommendations. The VASST study, a randomized controlled trial, assessed the effects of vasopressin versus norepinephrine in septic shock. It found no overall difference in mortality between the two groups. However, in less severe cases where norepinephrine doses were below 14 µg/min before randomization, vasopressin was associated with significantly lower mortality, suggesting potential benefits from early introduction of a second vasopressor. The VANISH trial failed to confirm this hypothesis, possibly due to broad inclusion criteria and unclear protocol regarding the combined use of both agents. Our hypothesis is that (1) vasopressin is beneficial when used synergistically with norepinephrine; (2) due to its negative effect on cardiac output (as shown in previous studies), vasopressin should only be administered to patients in the hyperdynamic phase of septic shock. The hypothesis is that the systematic addition of vasopressin to norepinephrine therapy in a hyperdynamic septic shock subpopulation would improve patient outcomes.

A Phase III, Open Label, Randomized, Controlled Study of VBI-S in the Treatment of Hypovolemia in Patients With Septic Shock (VBI-S-02)

This study is being conducted to evaluate the safety and effectiveness of VBI-S in elevating the blood pressure of septic shock patients with absolute or relative hypovolemia.

Neutrophil Activation and NETosis in Sepsis

This prospective observational study aims to evaluate neutrophil activation markers and circulating citrullinated histone H3 levels in adult patients with sepsis or septic shock.

Efficacy and Safety of Methylene Blue in the Treatment of Severe Septic Shock

The goal of this clinical trial is to investigate whether methylene blue injection can safely and effectively improve the survival rate of patients with severe septic shock, shorten the duration of norepinephrine use, reduce the dosage of vasopressors, promptly correct hemodynamics, and improve tissue perfusion and organ function impairment.

CytOSorb TreatMent Of Critically Ill PatientS Registry

Registry intended to provide a data repository and reporting infrastructure for the surveillance of CytoSorb device use in real-world critical care settings, and to serve as an objective, comprehensive, and scientifically-based resource to measure and improve the quality of patient care

Implementation of Timely Management of Sepsis and Septic Shock Protocol in the Emergency Department and Intensive Care Unit: A Quality Improvement Project at AFHJ

Study Title: Implementation of a Sepsis Management Protocol at Armed Forces Hospital Jazan (AFHJ). Purpose: The purpose of this quality improvement project is to determine if implementing a standardized, evidence-based "sepsis bundle" can improve the care and survival of patients with sepsis and septic shock in the Emergency Department (ED) and Intensive Care Unit (ICU). What the Study Involves: Researchers will implement a specific set of clinical guidelines based on the international Surviving Sepsis Campaign. This include: Using a scoring system (NEWS2 and SOFA) to identify sick patients earlier. Ensuring patients receive five critical treatments (the "one-hour bundle") within 60 minutes of diagnosis, including blood tests, IV fluids, and antibiotics. Comparison: The study will compare the outcomes of 74 patients treated before the protocol was introduced (the "Pre-protocol group") to 46 patients treated after the new protocol was put into effect (the "Protocol group"). Expected Outcome: The goal is to increase the number of patients who receive all necessary treatments within one hour from less than 15% to at least 60%. The study also aims to see if this protocol leads to shorter hospital stays and lower mortality rates.

Norepinephrine Equivalent Dose of Vasopressin, Phenylephrine and Epinephrine in Septic Shock

Septic shock is the most common form of circulatory shock encountered in patients admitted in intensive care unit. The initial management involves fluid resuscitation but if hypotension does not get resolved solely by it, then vasopressors become the mainstay of the management of shock to maintain adequate mean arterial pressure (MAP). Norepinephrine is recommended as the first line vasopressor in the management of septic shock as per Surviving Sepsis Campaign guidelines of 2021. It recommends addition of vasopressin to the regime if the target MAP is not achieved with just norepinephrine. However, in clinical practice various other vasopressors are being used in the management of septic shock, as per clinical condition. Different vasopressors have different modes of action and pharmacological effects on hemodynamics. Therefore, there evolved the need of development of a formula that would reflect the potency of each vasopressor in a standardized manner. Thus, the concept of Norepinephrine Equivalence (NEE) came into existence. In the recent years, different studies were conducted in various parts of the world with different primary objectives. These authors have proposed different formulas for calculation Norepinephrine Equivalence (NEE) dose of the used vasopressors as an inference from their studies. All these formulas are based on assumptions and there lacks standardization. There are presently no studies available in the existing literature, where a prospective study is done to primarily determine the Norepinephrine equivalence dose (NEE) of other vasopressors in patients of septic shock. Hence, the investigators aim to find out equivalent dose of these different drugs, which are being used commonly in the management of septic shock, in a prospective planned study.

Internal Jugular Vein and Inferior Vena Cava Collapsibility Indices as a Guidance of Fluid Responsiveness in Septic Shock Cancer Patients

This study aimed to compare between internal jugular vein and inferior vena cava collapsibility indices as a guidance of fluid responsiveness in septic shock cancer patients.

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.

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.

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

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.

Sepsis ICU Gut Microbiome Analysis

Sepsis is a life-threatening condition in which the body's response to an infection damages its own organs. This study aims to understand how the bacteria living in the gut change during sepsis and whether patterns of gut bacteria and chemicals found in stool can help identify patients at greater risk of death or poor recovery. This observational study plans to enroll approximately 180 adults with sepsis receiving care in the intensive care unit (ICU) at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. All participants will receive usual medical care. The study will not assign experimental treatments or change treatment decisions. Researchers will collect stool samples or, when stool is unavailable and sampling is safe, rectal swabs. Samples will be collected within the first 48 hours of the study, on days 3-5, on day 7, and near ICU discharge when feasible. Researchers will examine the types and amounts of gut bacteria. Samples from a selected group of participants will also be tested for chemicals related to metabolism. Information about illness severity, medicines, nutrition, and organ support will be collected from medical records. Participants will be followed for 90 days, using medical records and telephone follow-up. The main clinical outcome is death from any cause within 28 days. Other outcomes include death and unplanned hospital readmission within 90 days. Researchers will assess whether gut bacterial patterns add useful information to routine clinical assessments and compare findings with available data from other sepsis studies.

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.

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.

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.

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.