St Catharines

Researchers are evaluating different treatment strategies for patients hospitalized with Gram-negative bloodstream infections (GN BSIs) through the BALANCE+ trial. This adaptive platform trial uses an open-label, pragmatic design embedded in routine care to address important questions in managing GN BSIs, including antibiotic treatment duration, antibiotic de-escalation, oral antibiotic options, central line management, specific pathogen treatment, and follow-up blood cultures. The study builds on previous research and aims to improve patient outcomes and reduce antimicrobial resistance, a growing global health concern. The trial includes multiple treatment comparisons, such as de-escalation versus no de-escalation of antibiotics, oral beta-lactams versus non-beta-lactams, central vascular catheter retention versus replacement, cephalosporin versus carbapenem for low-risk AmpC organisms, and routine follow-up blood cultures versus no routine follow-up. Treatments are tailored based on blood culture results and clinical decisions, with specific protocols for antibiotic switching and catheter management. The trial uses Bayesian methods with interim analyses after every 1000 patients initially, then every 200 patients, and stops domains based on predefined criteria or sample sizes. Participants are patients admitted to hospitals with confirmed Gram-negative bacteremia who meet eligibility criteria for each domain. Assessments include monitoring for death, reinfection, readmission, and new antimicrobial resistance over 90 days, measured by the Desirability of Outcome Ranking (DOOR) scale. The trial incorporates detailed inclusion and exclusion criteria and collects data through routine clinical care, ensuring ongoing evaluation of treatment effectiveness and safety throughout the study period.

Researchers are evaluating the safety and effectiveness of ibrutinib combined with venetoclax (I+V) and ibrutinib alone in people with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This phase 2 study focuses on adjusting the ibrutinib dose either proactively or reactively based on side effects to find the best treatment approach. Participants will receive oral capsules of ibrutinib and, for some groups, oral tablets of venetoclax. The study includes different treatment groups to compare how these regimens work when ibrutinib dosing is modified in response to adverse events. Dosing schedules and adjustments will be closely monitored throughout the study. During the study, participants will undergo regular assessments including scans to measure lymph node size and other tests to track response and safety. Researchers will measure the best overall response rate for up to five years. Safety monitoring and follow-up will continue as needed to evaluate long-term outcomes and treatment tolerability.

Researchers are evaluating whether the medicine vicadrostat, combined with empagliflozin, helps adults with chronic heart failure (HF) who have a weakened heart pumping function, specifically a left ventricular ejection fraction (LVEF) below 40%. Eligible participants must have been diagnosed with chronic HF at least 3 months before joining. The study is a Phase III trial designed to compare the effects of vicadrostat plus empagliflozin against placebo plus empagliflozin in people with symptomatic chronic HF classified as New York Heart Association classes II to IV. Participants are randomly assigned to one of two groups. One group takes tablets containing vicadrostat and empagliflozin, while the other group takes placebo tablets that look like vicadrostat along with empagliflozin. Tablets are taken once daily for a period ranging from about 6 months up to about 3.5 years. Participants continue their usual heart failure treatments during the study. The study is double-blind, meaning neither the participants nor the study staff know who is receiving which treatment. During the study, participants regularly visit the study site or may have phone contacts for follow-up. They answer questions about their health and well-being. Doctors monitor and record any worsening of heart failure symptoms, hospital visits due to heart failure, or deaths. They also check participants' overall health and note any side effects. The main outcome measured is the time until a participant experiences cardiovascular death, hospitalization for heart failure, or an urgent heart failure visit, over up to 43 months of follow-up.

Researchers are investigating whether giving intravenous hyperoncotic albumin (20-25%) compared to normal saline boluses during renal replacement therapy (RRT) improves outcomes in critically ill patients with Acute Kidney Injury requiring RRT (AKI-RRT). This Phase 4 trial addresses the high risk of death and complications associated with severe AKI needing RRT, aiming to see if albumin can increase the number of days patients are free from organ support and RRT within 28 days after randomization. Participants will be randomly assigned to receive either albumin (20-25%) or normal saline as two 100 mL boluses during each RRT session in the ICU. The boluses are given at the start and halfway through the RRT sessions, which may include continuous RRT (CRRT), sustained low-efficiency dialysis (SLED), or intermittent hemodialysis (IHD). This treatment continues for up to 14 days while patients are receiving RRT. During the study, 856 ICU patients will be monitored for organ-support-free days over 28 days following randomization. Researchers will assess the safety and effectiveness of albumin by tracking how many days participants avoid organ support and RRT. The study includes careful monitoring of treatments, with randomization ensuring balanced comparison between albumin and saline groups across multiple Canadian hospitals and potentially other international sites.

Researchers are evaluating the use of non-vitamin K oral anticoagulants (NOACs) compared to no anticoagulation in people who have experienced transient atrial fibrillation episodes triggered by stress and have additional risk factors for stroke. This multinational, investigator-initiated Phase 4 trial aims to prevent stroke and other serious cardiovascular events in this group by assessing the effects of NOACs on two main outcomes: the occurrence of non-hemorrhagic stroke or systemic embolism, and a combination of vascular death and other major cardiovascular problems, over a follow-up period lasting until the last participant reaches 24 months of observation. Participants in the study are randomly assigned to either receive one of several NOAC medications—edoxaban, apixaban, dabigatran, or rivaroxaban—with dosing adjusted as needed and chosen by their prescribing doctor, or to receive no oral anticoagulation. The treatment continues throughout the follow-up period. The trial is open-label, meaning both researchers and participants know which treatment is given. The study specifically focuses on patients who had transient atrial fibrillation related to stress, such as after certain surgeries or acute medical illness. During the study, participants undergo regular monitoring to track the incidence of stroke, embolism, vascular death, heart attacks, blood clots, and other cardiovascular events. Researchers collect information over up to two years to evaluate these outcomes. Safety and adherence to treatment are also monitored. This thorough follow-up helps determine the impact of NOAC treatment compared to no anticoagulation in this particular patient population.

Researchers are evaluating the effectiveness of the antiviral drugs Paxlovid and Veklury in preventing long-term cardiovascular complications following COVID-19 infection in hospitalized adults. This is a phase 4, multicenter, double-blind, randomized placebo-controlled pilot trial called DEFEND. The study aims to assess the feasibility of recruitment and the accuracy of hospital outcome measures, focusing on events such as stroke, heart failure, venous thromboembolism, diabetes, or death within one year. Participants aged 18 and older who test positive for SARS-CoV-2 upon hospital admission and meet eligibility criteria will be randomly assigned to receive either Paxlovid orally twice daily for 5 days, Veklury intravenously once daily for 5 days, or a matching placebo, all alongside standard care. The trial will enroll about 118 participants across four hospitals in Ontario over a 12-month period, followed by a 12-month follow-up to monitor outcomes. During the study, participants will undergo monitoring for cardiovascular events and other health outcomes through hospital data and follow-up assessments. Researchers will track recruitment rates and evaluate the incidence of post-acute sequelae of COVID-19 over one year. The data collected will help design and conduct a larger future trial and inform clinical practice regarding antiviral use in this patient population.

Researchers are evaluating whether ziltivekimab can help people who were hospitalized due to a heart attack by potentially reducing the development of heart disease and preventing new heart attacks or strokes. This Phase 3 study compares ziltivekimab with a placebo, which is a dummy medicine that has no effect on the body. Both treatments are given by chance, with equal likelihood for participants to receive either ziltivekimab or placebo. Participants will inject the study medicine once a month under the skin in the stomach, thigh, or upper arm. Ziltivekimab is given as an initial loading dose followed by monthly maintenance doses. The placebo group receives a matching injection schedule. The study duration is about two years. During the study, researchers will monitor participants for the time until the first serious heart-related event, including cardiovascular death, non-fatal heart attack, or non-fatal stroke. Participants will be closely observed from the start of randomization up to 25 months. The study includes regular follow-ups to assess safety and effectiveness of the treatments throughout this period.

Researchers are evaluating whether two new immunotherapy drugs, botensilimab and balstilimab, can help patients with colorectal cancer that cannot be removed by surgery and is resistant to treatment. The study compares these drugs to the usual supportive care provided to improve quality of life. It also aims to see if these treatments slow tumor growth, shrink tumors, and identify markers in tumors or blood that predict benefits. Safety and how long the body takes to process these drugs are also being studied. Participants will receive either botensilimab and balstilimab or the best supportive care, which focuses on relieving symptoms and improving quality of life. Botensilimab is given as an intravenous infusion at 75 mg every 6 weeks for 4 doses, while balstilimab is given as 450 mg intravenously every 3 weeks. Those receiving supportive care will get treatments to help manage symptoms but not the investigational drugs. During the study, participants will be monitored for overall survival over 34 months. Researchers will assess quality of life, tumor response, and look for biological markers in tissue and blood. Safety will be closely followed, and participants must be available for treatment, follow-up, and completing questionnaires in English or French. The total study duration and treatment timelines are structured to ensure thorough evaluation of outcomes and safety.

The Canadian Critical Care Comparative Effectiveness Platform (CEPEC) is an international, multi-centered, randomized adaptive platform trial studying supportive care interventions commonly used in intensive care units worldwide. It focuses on evaluating vasopressors, platelet transfusions, nutrition, sedation, analgesia, and other treatments in critically ill patients. The study aims to provide better scientific evidence for these resource-intensive therapies that remain under-studied despite frequent use in ICUs. The trial includes several domains with specific interventions. In the Vasopressor Domain, participants receive vasoactive medications adjusted to different mean arterial pressure ranges (56-60, 61-65, 66-70, or 71-75 mmHg). The Platelet Domain investigates platelet transfusion thresholds before procedures, comparing transfusions given at platelet counts less than 10, 20, 30, 40, or 50 x 10^9/L. The Nutrition Domain compares enteral feeding given as three daily boluses versus continuous feeding over 24 hours. Each domain evaluates its respective treatment approach within the ICU setting. Participants will be closely monitored throughout their ICU stay, with outcomes measured including vasopressor use at hospital discharge up to 30 days, all-cause mortality at 90 days for the platelet domain, and recruitment rates over one year for the nutrition domain. Assessments include clinical evaluations, laboratory testing, and procedure monitoring. The study collects data on how these supportive care strategies affect patient outcomes, resource use, and safety during and after ICU treatment.

Atrial fibrillation and atrial flutter often occur after noncardiac surgery and can lead to serious long-term health problems. However, many patients with these conditions after surgery are not detected in routine clinical care. This research aims to find out how common important post-operative atrial fibrillation (POAF) is by using continuous heart monitoring for up to 14 days after surgery, within a 35-day follow-up period. Participants will wear a portable cardiac monitoring device that records their heart rhythm continuously for up to 14 days, starting within 72 hours after their noncardiac surgery. This device is designed to capture heart activity to help detect POAF early. The study includes patients who have undergone surgeries that cause significant physiological stress and require at least an overnight hospital stay or similar impact. During the study, patients will be closely observed for signs of atrial fibrillation or flutter using the device. Researchers will track the incidence of these heart rhythm problems within 35 days after surgery. The study involves detailed monitoring and data collection to improve understanding of POAF, with participants followed to assess heart rhythm changes and related health events during the monitoring period.