Clinical Research Directory

Rezafungin Peritoneal Diffusion for Intra-abdominal Candidiasis

ntra-abdominal candidiasis is a serious infection common in critically ill patients, often leading to high mortality if not treated quickly. Standard antifungal treatments may be less effective due to growing resistance and poor drug penetration into the abdominal cavity. In critically ill patients, drug levels can vary widely due to factors like surgery, inflammation, fluid resuscitation, or extracorporeal support, increasing the risk of underdosing. Rezafungin is a new antifungal agent with a long half-life and broad activity against Candida species, offering potential advantages in this setting. However, there is currently no data on its concentration or effectiveness in the peritoneal fluid of patients with intra-abdominal sepsis. Its long half-life, coupled with repeated pharmacokinetic variations in critical care settings and the risk of insufficient concentrations, may hinder its use in this population.

Effects of Donor-recipient Sex-matched Blood Transfusion on Patient Outcomes

Red blood cell (RBC) transfusions are selected based upon matching donor and recipient blood group: donor and recipient sex are not considered when selecting blood for transfusion. Hence, transfused patients can currently receive sex-matched and/or unmatched RBCs when transfusions are given. Sex-matched stem cell transplants, and some solid organ transplants, have shown that sex-matching donor to recipient improves patient outcomes. Recent exploratory studies have also suggested that patient outcomes could be improved by sex-matching for RBC transfusion. There is emerging evidence of underlying biologic mechanism(s) to support these observations. This study is designed as a randomized controlled trial and will explore the impact on patients who receive RBC transfusions from donors of the same sex ("sex-matched") compared with donors of the opposite sex ("sex-mismatched"). The trial will study adult patients admitted to the Intensive Care Unit who require an RBC transfusion. Patients will be assigned (through a process called randomization) to receive sex-matched RBCs or sex-mismatched RBCs to determine if there is a difference in mortality between those receiving matched versus mismatched RBCs. The results of this trial could have direct implications on resources, blood inventory, and RBC transfusion ordering practices.

Accuracy and Safety of the Syai Tag System for Continuous Glucose Monitoring in Intensive Internal Care Unit

Researchers at the Department of Intensive Internal Medicine and the Department of Endocrinology and Diabetology will conduct a study to verify the accuracy and safety of the new Syai Tag system for continuous glucose monitoring in patients in intensive internal care. Almost 150,000 people in Slovenia have diabetes, so keeping a close eye on blood sugar levels is key to preventing complications. The new sensors for continuous monitoring are available over the counter and certified as medical devices. The study will include at least 100 patients who will need blood sugar monitoring during their stay in the intensive care unit. Each patient will have two small sensors placed on each upper arm to continuously measure their blood sugar levels, but these values will not be visible to medical staff. At the same time, healthcare professionals will perform routine blood sugar measurements, and researchers will then compare the accuracy of both methods. The procedure is safe and painless, and patients will receive the same quality of care as usual.

SOFA-2 Score in Turkish ICUs

This study aims to evaluate how well a new scoring system called the Sequential Organ Failure Assessment-2 (SOFA-2) works in adult intensive care units in Türkiye. SOFA-2 is designed to measure the severity of organ dysfunction in critically ill patients using routinely collected clinical and laboratory data. It is an updated version of the original SOFA score and reflects modern intensive care practices. In this multicenter observational study, adult patients admitted to participating intensive care units will be followed during their ICU stay. SOFA and SOFA-2 scores will be calculated during the first 24 hours of admission, and in patients with longer stays, additional scores will be recorded. No additional tests or treatments will be performed as part of the study. The main goal of the study is to examine the relationship between SOFA-2 scores and intensive care unit mortality. The results are expected to help clinicians better assess disease severity and outcomes in critically ill patients.

Quality Improvement Intervention for a Safe Antimicrobial Use Reduction in Critically Ill Patients

The goal of this clinical trial is to learn if an educational intervention with audit and feedback on physicians and health care professionals who participate in antimicrobial treatment decisions can reduce the use of antimicrobials in adult patients admitted to a sample of Brazilian intensive care units (ICUs). The educational intervention is based on a literature review of current recommendations for a more rational use of antimicrobials and microbiological tests in daily ICU practice. The main questions it aims to answer are: * Does the educational intervention reduce the antimicrobial consumption in the intensive care units? * Does this educational intervention aiming to reduce antimicrobial utilization in accordance with the latest guidelines have any safety signals regarding ICU mortality rates or ICU length-of-stay? Researchers will compare (1) ICUs sequentially randomized to this quality improvement educational intervention aimed at improving antimicrobial utilization to (2) the same ICUs at months where the educational intervention has not been delivered yet. Each participant ICU will transition to the quality improvement intervention approximately each month, starting at July, 2025. This quality improvement intervention is based on current recommendations for antimicrobial stewardship from regulatory agencies and medical societies, including cognitive aids for physicians to improve decision-making regarding the commencement of antimicrobials, their duration and antimicrobial time-outs. The investigators hypothesize that intensivists (ICU doctors) need to embrace antimicrobial stewardship as a core competence of their daily activities.

Ketamine Sedation in the ICU (KANINE) RCT

Sedation is given to intensive care unit (ICU) patients to treat discomfort, anxiety, agitation, and to help facilitate care, particularly when they require a breathing tube. Sedation is very commonly used in the ICU with North American data showing almost 40% of ICU patients get sedation to help when they are requiring a breathing machine. Various medications can be given intravenously to provide sedation in the ICU but there are side-effects associated with each such as decreasing a patient's own drive to breathe, and delirium or acute confusion, both of which are associated with worse outcomes. Also, most drugs used for sedation don't treat pain. As a result, many ICU patients are also given narcotics for pain control which can result in tolerance, dependence, and withdrawal. Ketamine is a sedating medication that also treats pain and is often used in the Emergency Department and in the Operating Room but for whatever reason is not commonly used in the ICU. The investigators are proposing a study to examine the usefulness and safety of adding an intravenous infusion of ketamine to usual care in adult patients that are on a breathing machine in the ICU. Study Methods The KANINE study is being done at hospitals across Ontario, Canada. It is a randomized controlled trial which means patients will be randomized (akin to a coin flip) to receive ketamine or usual care without ketamine. The study will be blinded which means that neither patients or the doctors will know if the patient is getting ketamine or not, those that get randomized to usual care without ketamine will get an intravenous solution that looks the same as the ketamine infusion. This is important to make sure the results aren't biased in any way. The investigators will include adult ICU patients on a breathing machine who are early in their ICU admission. As most patients will be unconscious, the investigators will ask substitute decision makers (families or caregivers) of patients for informed consent prior to the study commencing. Regardless of whether patients get randomized to ketamine or not, the investigators will make sure that all patients will be adequately sedated and have their pain managed as per usual care. Setting This study will be performed in adult ICUs across Canada. Population The investigators will include adults admitted to the ICU on a breathing machine and expected to remain mechanically ventilated beyond the calendar day after randomization. The investigators will exclude patients if: (i) they were admitted with a brain bleed, traumatic brain injury, or stroke; (ii) Admitted with uncontrolled high blood pressure; (iii) admitted with status asthmaticus; (iv); admitted to the ICU with partial thickness burns greater than 10% total body surface area or any full thickness burns; (v) if they have a history of schizophrenia; (vi) if they have very bad liver failure; (vii) if they are palliative or only for comfort care; (viii) if they are requiring very high doses of blood pressure support medication to increase their blood pressure; (ix) if they are receiving a medication that causes paralysis, sometimes used in patients with very bad lung disease; (x) if they have a tracheostomy which means a whole in their neck that they breathe through; (xi) if they are allergic to ketamine; (xii) if they've had a liver transplant in the last month; (xiii) if they are pregnant or breast-feeding. Outcomes The investigators will follow all the study patients to see if their outcomes are different depending on whether they get randomized to ketamine or not. The investigators will capture how much time they are on the breathing machine, whether they survive or die, how long they stay in the ICU and whether they require a tracheostomy which is a procedure often done on patients who require the breathing machine over a prolonged period of time. The investigators will also capture how often they get delirious and for those that get delirious how long it lasts for. The investigators will capture how much of other sedating medications study patients use such as antipsychotics and benzodiazepines. The investigators will capture outcomes such as how often study patients get post-traumatic stress disorder after leaving the ICU and how well their pain relief is addressed during their ICU stay. Finally, the investigators will capture side effects related to ketamine or other sedating drug use.

Continuous Passive Motion to Prevent Ankle Contracture and Muscle Atrophy in Ventilated Patients

This clinical trial aims to evaluate whether continuous passive motion (CPM) can prevent ankle joint contracture and muscle atrophy in critically ill patients receiving mechanical ventilation in the ICU. The study will also assess the feasibility and safety of implementing CPM therapy in this population. The primary objectives are: To determine whether CPM preserves ankle dorsiflexion range of motion during ICU immobilization. To assess whether ultrasound can detect changes in tibialis anterior muscle morphology in response to CPM. In this within-subject design, each participant will receive CPM therapy on one ankle while the contralateral ankle serves as the control. Outcomes related to joint mobility and muscle condition will be compared between the two sides. Participants will: Receive CPM treatment on one ankle for 30 minutes, twice daily, for up to 7 days or until ICU discharge. Undergo goniometric and ultrasound assessments at baseline and after the intervention. Continue to receive standard ICU care throughout the study period.

Phosphate Urine Excretion in Critically Ill Patients

Hypophosphatemia is a common disorder in critically ill patients, appearing in 15-35% of Intensive Care Unit (ICU) admissions. Its reasons are multifactorial, including sepsis, refeeding syndrome, and continuous renal replacement therapy. Hypophosphatemia is generally accepted as a predictor of poor outcomes, such as prolonged ventilation and higher mortality. However, conflicting evidence exists and several works demonstrated no effect on length of ventilation, nor mortality. We have recently demonstrated no effect of hypophosphatemia on mortality and length of ventilation. However, both parameters were affected by energy delivery to the patient, with higher energy delivery associated with lower mortality and longer length of ventilation, suggesting a complex interaction between energy delivery to the patient, hypophosphatemia appearance, and patient outcomes. This raised hypothesis that hypophosphatemia is a marker of recovery, as in fulminant hepatic failure, or recovery after hepatectomy. Phosphate is mainly an intracellular anion, with only 1% of its total body amount is extracellular. It is absorbed from the small intestine, mainly at the jejunum, both through passive para-cellular and active trans-cellular process. Phosphate is excreted in the urine, after being filtered in the glomeruli, and reabsorbed mainly in the proximal tubule (less than 10% of the reabsorption occurs in the distal nephron), by sodium-phosphate co-transporters. Phosphate regulation in the body is complex. It is regulated by vitamin D, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF-23). Therefore, phosphate regulation is affected both from intestine dysfunction and kidney injury. Although hyperphosphatemia in various kidney injury is well described, the effect of kidney function regarding phosphate excretion in critically ill patients with hypophosphatemia has been scarcely described. French and Bellomo described 7 patients who had decreased phosphate kidney reabsorption during hypophosphatemia. Charrone et. al demonstrated increased phosphate excretion after IV phosphate infusion to 47 critically ill patients with hypophosphatemia. Dickerson et. al demonstrated higher rates of hypophosphatemia in 20 thermally injured patients (compared to 20 multiple trauma patients) despite greater phosphate delivery through nutrition, along with increased (although insignificant) phosphate urinary excretion in this group. This might suggest that increased renal phosphate loss has a role in hypophosphatemia development. Better understanding these processes is important, with regard to the effect of nutritional support and hypophosphatemia effects on patients' outcomes. This study aims to describe urinary phosphate excretion in critically ill patients with regard to kidney function, phosphate serum level, and phosphate intake.

Blood DdPCR for Early Identification and Dynamic Surveillance of Pathogenic Bacteria in ICU Septic Patients: a Single-centre, Prospective, Observational Study

The purpose of this study is to investigate the efficacy of droplet digital PCR (ddPCR) in identifying pathogenic organisms in ICU sepsis patients, aiming to find a method that allows early identification of pathogenic organisms and dynamic surveillance in order to assess the association between pathogenic species and loads and clinical characteristics and outcomes.