Clinical Research Directory

Development of Context-Adapted Quality Indicators for Early Sepsis Care in Sub-Saharan Africa - A Modified Delphi Consensus Procedure

The research project is an anonymous, prospective, non-interventional consensus study in the form of a modified Delphi method, consisting of three online surveys and structured feedback meetings without recording. The goal is the structured evaluation and consolidation of expert assessments to develop context-adapted quality indicators and operationalize them for early sepsis care in Sub-Saharan Africa.

EARLY-SARDS: Early AlveolaR Lung biologY Underling Sepsis-Associated ARDS

Sepsis-associated acute respiratory distress syndrome (ARDS) remains a major cause of respiratory failure and mortality in critically ill patients. Although only a proportion of patients with sepsis develop ARDS, early identification of those at highest risk remains a major unmet clinical need. Current prediction relies largely on clinical deterioration and oxygenation impairment, which often occur when lung injury has already developed. Increasing evidence suggests that biological responses to sepsis are compartmentalized between the systemic circulation and the alveolar space, while early abnormalities in respiratory mechanics and ventilatory efficiency may provide complementary information on evolving lung injury. However, no prospective study has integrated serial systemic and alveolar biomarkers with bedside respiratory physiology during the earliest phase of sepsis-associated respiratory failure. EARLY-SARDS is a prospective observational cohort study designed to characterize the early biological and physiological trajectories of invasively ventilated patients with sepsis or septic shock. Serial bronchoalveolar lavage (BAL) and plasma samples, together with standardized measurements of respiratory mechanics and gas exchange, will be collected during the first 96 hours after enrollment. The primary objective is to develop an integrated biological-physiological model capable of predicting ARDS development and subsequent peak ARDS severity. Secondary objectives include characterizing biological compartmentalization, identifying integrated biological-physiological subphenotypes, and evaluating their association with clinically relevant outcomes, including duration of mechanical ventilation, ventilator-free days, need for extracorporeal respiratory support, ICU length of stay, and mortality.

T6A Biomarker for Detection of Bacterial Infection in Newborn Infants

This bi-center study aims to assess the efficacy of a new biomarker, N6-threonylcarbamoyladenosine (t6A), for the early diagnosis of Early-Onset Sepsis (EOS) in newborns.

NAI (Nogapendekin Alfa Inbakicept) Plus Standard of Care in Critically Ill Adults With Sepsis

This study will test whether adding an immune-stimulating drug, nogapendekin alfa inbakicept (NAI), to standard intensive care treatment is safe and potentially helpful for adults with sepsis or septic shock. All participants will receive usual sepsis care. They will also get NAI as an injection under the skin on Day 1, and again on Days 14 and 21 if still in the hospital (and with low lymphocyte counts on Day 21). The study will first focus on safety in 10 patients, then enroll more (total 49) to see how many are alive at 28 days and 90 days, how their white blood cell counts recover, how much organ support they need, and how long they stay in the ICU and hospital.

EAA-Guided AN69-oXiris and PMX-HP Therapy in Septic Patients

Sepsis and septic shock are life-threatening conditions in which the body's response to infection can cause dangerously low blood pressure and organ failure. In some patients with an infection inside the abdomen, severe inflammation may continue even after emergency surgery or another procedure has controlled the source of infection. Endotoxin is a substance produced by certain bacteria that may worsen this inflammation. The Endotoxin Activity Assay is a blood test that estimates how strongly endotoxin is affecting the body. This study will compare two blood purification treatments, AN69-oXiris and polymyxin B hemoperfusion (PMX-HP), in patients receiving intensive care for sepsis or septic shock caused by an intra-abdominal infection. Blood purification removes blood through a central venous catheter, passes it through a special filter or cartridge, and then returns it to the body. These treatments are intended to reduce endotoxin or other substances involved in inflammation. The study plans to enroll 50 participants at Seoul St. Mary's Hospital. Participants will be assigned by chance, in a 1:1 ratio, to receive either AN69-oXiris or PMX-HP. Participants and the clinical team will know which treatment is used.

Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Exploratory, Bayesian Basket Trial

PALETTE is a perpetual adaptive platform to efficiently study sepsis interventions within 'treatable traits' in all-ages patients enabling prompt evaluation of pandemic treatments. Treatable traits, therapeutic targets identified by phenotypes or endotypes (defined by biological mechanism or by treatment response) through validated biomarkers (measurable characteristic reflecting normal or pathogenic processes, or treatment responses), may include multi-omics, cellular, immune, metabolic, endocrine features, or intelligent algorithms. PALETTE Bayesian adaptive design enables parallel investigations of multiple interventions for sepsis, and quick inclusion of pandemic pathogens. PALETTE's new conceptual model will respond to the challenges of standard approaches, i.e. series of sepsis trials, each investigating one or two interventions, expensive, time consuming, and inappropriate in pandemic context.

Differential Clinical Phenotypes Of Early CD4+ And CD8+ T-Cell Recovery And Association With 28-Day Mortality In Sepsis Patients

This is a retrospective non-interventional cohort study. Medical records of adult patients with sepsis admitted to the intensive care unit will be retrospectively reviewed. We aim to compare clinical manifestations, laboratory indicators and prognosis among different sepsis phenotypes, so as to provide clinical reference for early identification and risk stratification of sepsis. No intervention will be performed on patients in this study.

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.

Effects of Paroxetine on Cardiovascular Function in Septic Patients

It is known that septic shock is characterized by arterial hypotension, decreased peripheral vascular resistance and hyporeactivity to vasoconstrictor agents, with NO being an important mediator of this organ dysfunction. Data in the literature have shown that hyporeactivity to catecholamines is associated with a decrease in the density of α and ß receptors in the aorta and heart, respectively, as well as an increase in GRK2 levels and that NO contributes to the increase of this kinase in sepsis . Based on this, it is hypothesized that cardiac dysfunction and decreased peripheral vascular resistance observed in sepsis may result from an increase in GRK2 activity and/or expression and its inhibition may be a relevant therapeutic target in septic shock patients. Based on this line, a measurable clinical benefit of paroxetine through the regulation of GRK2 expression in patients with septic shock is postulated.

Dynamics of Organ Damage and Immune Exhaustion During Sepsis

This is a prospective, non-randomized study investigating if organ damage and immune changes can be measured by liquid biopsy NGS through advanced analytical methods.

ICU-SUCCEED for Survivors of Acute Respiratory Failure and Their Caregivers

This study will investigate whether a family-centered intervention that has been adapted for patients with critical illness and their caregivers is possible, acceptable, and helpful

A Study to Learn About How Safe BAY 3389934 is, Its Suitable Dose, and How it Affects the Participants With Sepsis Induced Coagulopathy

Researchers are looking for a better way to treat people who have sepsis induced coagulopathy. Sepsis happens when bacteria and their toxins spread in the blood, causing an infection. To overcome the infection the body responds activating the immune system, sometimes this immune response is too active and causes uncontrolled blood clot formation, also called sepsis-induced coagulopathy. Sepsis coagulopathy damages blood vessels and organs and leads to low platelet levels in the body. In severe cases, it can even lead to death. The main purpose of this first in patient study is to learn about how safe BAY 3389934 is, its suitable dose, and how it affects the participants with sepsis induced coagulopathy. For this study, researchers will enroll people receiving treatment for sepsis induced coagulopathy in a hospital intensive care unit (ICU). For this, the researchers will collect the number of participants with medical problems during and after receiving BAY 3389934. These medical problems are also known as "adverse events". Doctors keep track of all medical problems that happen in studies, even if they do not think they might be related to the study treatments. Participants will be divided into 2 groups. The first group will receive the lowest starting dose of BAY3389934. The researcher will carefully monitor how the participant responds to the medication and may adjust the dose, either increasing or decreasing it based on the safety and the tolerability of the drug. If no serious side effects are reported from the first group, the second group will receive higher dose of BAY3389934. Each participant will be in the study for around 28 days. During the study, the doctors and their study team will: * Take blood and urine samples, * Do physical examinations, * Check vital signs such as body temperature, blood pressure and heart rate, * Examine heart health using electrocardiogram (ECG)

Discordance Between Capillary Refill Time and Oxygen Extraction Ratio in Septic Shock

In septic shock, restoring large-vessel (macrocirculatory) perfusion-reflected by a normal capillary refill time (CRT)-does not always mean that oxygen use at the tissue level has recovered. This mismatch, sometimes called loss of hemodynamic coherence, may be detectable by comparing CRT with the oxygen extraction ratio (O₂ER), a marker of how much oxygen the tissues are extracting from the blood. Patients whose CRT has normalized but whose O₂ER remains abnormal-either too high (suggesting oxygen delivery that is insufficient for demand) or too low (suggesting microcirculatory shunting)-are considered to have a "discordant" perfusion phenotype. This prospective, single-center, observational cohort study aims to determine how often this CRT-O₂ER discordance occurs at the 6th hour of resuscitation in adult patients with septic shock, and whether it is associated with 28-day mortality. Approximately 100 consecutive adult patients diagnosed with septic shock (with pre-existing central venous and arterial catheters) will be followed. Clinical and laboratory measurements-including CRT, O₂ER, lactate, mottling score, and organ dysfunction scores-will be recorded at hours 0, 6, 12, and 24, with the main phenotype grouping performed at hour 6. The study is purely observational: CRT is a painless, non-invasive bedside measurement, and O₂ER is calculated from blood gas samples already drawn as part of routine care, so no additional interventions or blood draws are performed for research purposes.

Dysfunctional Myelopoiesis and Myeloid-Derived Suppressor Cells in Sepsis

Adverse outcomes in surgical sepsis patients are secondary to dysregulated emergency myelopoiesis, and expansion of myeloid-derived suppressor cells. Here we propose to determine the underlying mechanisms behind the increased expansion of these leukocyte populations and the underlying mechanisms that drive inflammation and immune suppression.

Limited Versus Extended Trophic Feeding (LET-FEED) Trial

Study Hypothesis/Question In infants born very preterm, advancing enteral feeds after 24 hours from birth (limited trophic feeds) versus after 72 hours (extended trophic feeds) reduces the risk of all-cause late onset sepsis (LOS) without increasing the risk of other adverse outcomes. Study Design Type This is a multi-center, open-label, parallel-group, individual randomized controlled trial comparing two different trophic feeding regimens in preterm infants born between 25w0d and 31w6d. These infants will be randomly assigned to either the intervention group, receiving limited trophic feeding (20 to 25 mL/kg/day for one day) or the control group, receiving extended trophic feeding (20 to 25 mL/kg/day for three days) prior to advancing enteral feeds until full feeding volume (140 mL/kg/day) is achieved. Eligibility Criteria Preterm infants with gestational ages between 25 0/7 and 31 6/7 weeks and a birthweight of \<1500 grams who are admitted to six participating neonatal units will be eligible for inclusion. Infants with \<5th percentile for weight at birth, vasopressor use within first 24 hours of life major congenital/genetic anomalies affecting enteral feeding, growth, or mortality, and those with a terminal illness in which decisions to withhold or limit support have been made will be excluded. Infants of parents or legal guardians who are unable to provide consent within 36 hours of birth will also be excluded. Study Intervention/Methods Written parental informed consent will be obtained prenatally or within the first 36 hours of birth. Infants will be randomized to receive limited trophic feeds of 24 to 36 hours or extended trophic feeds for 72 hours prior to the advancement of enteral feeds. Infants will be fed parent's own milk (POM) with donor human milk as the alternative if POM is unavailable. Primary Outcome Late-onset sepsis, defined as positive blood, urine, and/or cerebrospinal fluid (CSF) cultures in the presence of compatible clinical signs of sepsis, occurring after postnatal day 3 and before hospital discharge, and treated with antibiotics for 5 days or more. Secondary Outcome(s) The trial will assess various secondary outcomes including length of hospital stay, all-cause in-hospital mortality, duration of IV fluids and central line utilization, necrotizing enterocolitis (Bell's stage IIa or higher), severe intraventricular hemorrhage (grade III or IV either unilaterally or bilaterally), bronchopulmonary dysplasia (oxygen requirement or positive pressure ventilation at 36 weeks corrected gestational age), or retinopathy of prematurity requiring intervention. Additionally, growth metrics throughout hospitalization will be evaluated using change in weight, length, and head circumference z-scores from birth to 36 weeks' corrected gestational age between infants in the limited and extended trophic feeding groups. We will also evaluate the 2 year developmental outcomes of a subset of participants who consent to follow up. This will include the Bayley Scales of Infant and Toddler Development-4th edition Language, Cognitive, and Motor domain scores at 2 years corrected age.

Validation of SOFA-2 for Mortality and Sepsis-3 Prevalence in Turkey

The goal of this observational study is to validate the effectiveness of the new SOFA-2 score in predicting mortality and to determine the current frequency of sepsis in adult patients admitted to Intensive Care Units (ICUs) in Turkey. The main questions it aims to answer are: * Does the SOFA-2 score accurately predict 30-day mortality in ICU patients? * What is the prevalence of Sepsis-3 and septic shock in Turkish ICUs? Researchers will compare the new SOFA-2 score to the existing SOFA-1 score to see if the new score provides better predictive accuracy for patient outcomes. Participants will not receive any experimental intervention. Researchers will collect data from routine medical care, including: * Vital signs, laboratory test results, and details of organ support (such as mechanical ventilation or dialysis) during the first 24 hours of admission. * Survival status at 30 days.

Pharmacokinetics and Pharmacodynamics of Ceftazidime in Pediatric ICU Patients

Mortality benefit has been proven with early antibiotic administration in sepsis. Antimicrobial therapy should be based on early achievement of effective drug concentrations by optimizing the pharmacokinetic/pharmacodynamics of individual drugs. Optimal dosing in the critically ill patient can be challenging with the rapidly changing physiology of sepsis during the first days of hospitalization with capillary leak, fluid overload, changes in cardiac output, and alterations renal clearance. Ceftazidime is the preferred beta-lactam for empiric treatment of sepsis at Lurie Children's Hospital because of its anti-pseudomonal and anti-enteric bacilli coverage, however, the majority of pharmacokinetic data currently published in pediatrics does not include Intensive Care Unit (ICU) patients. Adult pharmacokinetic/pharmacodynamics data suggest that critically ill adults with high level of illness severity may benefit from continuous or extended infusion beta lactam therapy to optimize the therapeutic concentration particularly for pathogens that are relatively resistant to beta-lactams. Understanding the changing pharmacokinetic/pharmacodynamics of ceftazidime with the progression of illness in the ICU may help determine if current dosing regimens are adequate to maintain appropriate drug concentrations to optimize antimicrobial treatment.

A Study on How the Immune System Responds to Sepsis and Its Long-term Effects

Sepsis occurs when an infection, caused by bacteria, a virus, or a fungus, enters the body and throws the immune system out of balance. Instead of protecting the body, the immune response may become too strong and start damaging healthy organs, or it may become too weak and fail to control the infection. Both situations can be life-threatening. Even people who survive sepsis may experience long-term health problems, such as new infections, heart and blood vessel diseases, or early death. This study aims to better understand how the immune system behaves during and after sepsis. We believe that there are different types of immune responses in sepsis, called immunotypes. We will identify these immunotypes by examining substances in the blood and changes in immune cells. We will then study which immunotypes help protect patients and which may cause short- or long-term harm. Understanding these immunotypes may make it possible in the future to quickly determine what type of immune response a patient with sepsis has. This could help doctors choose the best treatment for each individual patient. A total of 400 patients with sepsis from the intensive care unit will take part in this study. We will collect blood samples at several time points and gather information about their health. Participants will be followed from their intensive care admission until one year after they return home.

Evaluation of Pediatric eCART Implementation

This is a study comparing 3 years of retrospective data (pre-implementation) to 2 years of prospective data after the implementation of a pediatric version of Electronic Cardiac Arrest Risk Triage (pediatric eCART), a clinical decision support (CDS) tool that uses electronic health records (EHR) to identify patients with high risk for life threatening outcomes. Up to 30,000 encounters with pediatric patients will be assessed. Acceptability of the pediatric eCART intervention will also be measured from pediatric nurse clinicians.

Call for Life Sepsis

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-attributable mortality in sub-Saharan Africa (sSA) is high, with in-hospital mortality in some settings approaching 40%. Studies show that mortality among children under 5 years hospitalized with sepsis remains high within the first 6 months of discharge. Additionally, high mortality has been observed among other populations within sSA, with factors such as HIV infection being associated with increased risk. Reducing sepsis deaths contributes to the achievement of the Sustainable Development Goals (SDG), particularly SDG 3 in reducing maternal mortality (3.1), neonatal and under five mortality (3.2), and burden of mortality from communicable diseases (3.3) and improving universal health coverage (3.8). The World Health Organization (WHO) has recognized sepsis as a global priority, with low- and middle-income settings being particularly affected. In sSA, sepsis is commonly associated with infectious diseases like malaria, Human Immunodeficiency Virus/ Acquired Immunodeficiency Syndrome (HIV/AIDS), pneumonia, tuberculosis, and diarrhea. Guidelines from the Surviving Sepsis Campaign (SSC) have become standard in some settings. However, little is known about patients' status post-discharge. This study aims to evaluate two post-discharge follow-up strategies for adult sepsis patients. Study duration is 45 months, participants will receive intervention up to 90 days post discharge. Description of intervention: Post-discharge follow-up strategy 1: Enhanced Discharge Intervention (EDI) Post-discharge follow-up strategy 2: EDI plus Interactive Voice Response (IVR) \*All participants will receive a feature phone. Objectives: The study aims to evaluate two post-discharge follow-up strategies for adult patients hospitalized with sepsis, focusing on their efficacy in reducing the 90-day mortality, and their effect on return to follow-up, number of re-admissions, and quality of life. Primary efficacy endpoint * 90- day all-cause mortality post discharge Secondary end points * Time to death * 28-day all-cause mortality * Attendance within 14-day check-up post discharge * Re-admission within 28 and 90 days * Days alive and out of hospital (DAOH) * Quality of life score (Baseline vs 28 day and Baseline vs 90 days) * Differences in baseline demographic and clinical characteristics (e.g., age, sex, disease severity, comorbidities, key laboratory values) between randomized participants and screen failures. Study design: This is an open-label, randomized, parallel, interventional study, with two post-discharge follow-up strategies: 1) EDI; or 2) EDI plus IVR system. Fixed allocation randomization at a 1:1 ratio will be applied to either study arm. Sample size: A total of 1,410 (705 per arm) from the four countries (Uganda, Nigeria, Ghana and Mozambique) will be enrolled competitively across the sites.

Early Sepsis Recognition Tool

This study seeks to develop early recognition tools specially designed for children meeting the Phoenix definition and explore implementation science aspects by investigating facilitators and barriers to adopting Phoenix sepsis criteria in clinical practice. This addresses the critical need for systemic, evidence-based approaches to paediatric sepsis identification across diverse healthcare settings in Asia.

Triage Performance and Physiological Predictors of Serious Illness in Febrile Children in the Pediatric Emergency Department

This multicenter prospective observational cohort study evaluates how well the initial triage category assigned by the Turkish Ministry of Health three-level color-coded triage system (Red-Yellow-Green) predicts serious clinical outcomes in children aged 0-18 years who present with fever to pediatric emergency departments. The study additionally assesses whether physiological parameters recorded at triage (heart rate, respiratory rate, oxygen saturation, capillary refill time, AVPU level of consciousness, and general appearance) provide independent and incremental prognostic value beyond the assigned triage category. Ten centers across Turkey will enroll consecutive eligible febrile children over a 3-month period. Routine clinical care and triage decisions are not altered by the study. The primary outcome is a composite serious clinical outcome. The study is reported in accordance with the STROBE and TRIPOD statements.

İntensive Care Sepsis Prevelance in Turkey (INSEP-TURK)

Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, leading to tissue damage, multiple organ dysfunction (MODS), disseminated intravascular coagulation (DIC), and high mortality. Despite its global significance, robust epidemiological data from low- and middle-income countries, including Turkey, remain limited. This multicenter, two-timepoint point-prevalence study aims to determine the prevalence of sepsis and septic shock in adult intensive care units (ICUs) across Turkey and to evaluate associated clinical outcomes.The study will be conducted between September 2025 and January 2026 in adult ICUs nationwide. Sepsis and septic shock will be defined according to the 2021 Surviving Sepsis Campaign Guidelines. Detailed data will be collected on participating ICUs, clinicians, patient demographics, comorbidities, infection characteristics, organ dysfunction, laboratory findings, and treatments. Patients will be followed for 30 days to assess ICU length of stay, discharge status, mortality, and ventilator- and vasopressor-free days.The primary objective is to determine the point prevalence of sepsis and septic shock in Turkish ICUs. The secondary objective is to evaluate 30-day mortality among patients with sepsis and septic shock. The findings are expected to provide crucial epidemiological insights and help improve sepsis management strategies in Turkey.

Correlation of Memory CD8+ T Cells With Sepsis Severity and Mortality: a Single-center, Unblinded, Prospective, Non-interventional, Observational Study

Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Severe sepsis is the most common cause of death among critically ill patients in non-coronary intensive care units (ICU). Sustained excessive inflammation and immune dysfunction have been confirmed to play a key role in organ damage and early death of sepsis patients. Therefore, it is important to reduce excessive inflammatory response mediated by immune cells and pro-inflammatory cytokines in the acute phase of sepsis. Single-cell RNA sequencing performed on both septic patients and mice suggest that changes in Tcm (CD3+ CD8+ CD44+ CD127+ CD62L+) and Tem (CD3+ CD8+ CD44+ CD127+ CD62L -) in the acute phase of sepsis may play an important role in sepsis. In addition, animal researches showed that Tcm and Tem decreased decreased continuously at 24, 48 and 72h after cecal ligation and perforation (CLP) in mice, and the adoptive transfer of Tcm , sorting from spleen of mice 24h after CLP , but not Tem improved 7-day survival rate of sepsis mice. This observational study is aimed to investigate the quantity and proliferation of Tcm and Tem in the acute phase of sepsis and their correlation with severity level and mortality of septic patients in ICU.