St Catharines

Researchers are evaluating various treatment strategies for Gram-negative bloodstream infections GN BSIs in a large, ongoing platform trial called BALANCE. This trial aims to improve treatment methods, patient outcomes, and reduce antimicrobial resistance. It builds on previous research and uses an adaptive design to answer critical questions about managing these serious infections in hospitalized patients. The trial studies different treatment approaches including antibiotic de-escalation, oral beta-lactam versus non-beta-lactam antibiotics, whether to replace or retain central vascular catheters, selecting cephalosporins or carbapenems for specific bacteria, and the use of routine follow-up blood cultures. Participants are randomly assigned to one of these treatment strategies within each domain, with ongoing adjustments based on interim analyses. The initial pilot study has completed, and all patients from that phase are included in the main trial. Participants will be monitored over 90 days for outcomes including death, reinfection, hospital readmission, and development of new antimicrobial resistance. Evaluations include laboratory tests, clinical assessments, and tracking of antibiotic use and patient health status. The trial uses a ranking scale combining these outcomes to determine the desirability of each treatment strategy. This adaptive platform design allows continuous learning and refinement of treatments to improve care for people with GN BSIs.

Researchers are evaluating the use of intravenous hyperoncotic albumin compared to normal saline boluses in critically ill patients suffering from Acute Kidney Injury requiring renal replacement therapy AKI-RRT. This trial aims to determine whether albumin administration during renal replacement therapy sessions increases organ support-free days and renal replacement therapy-free days within 28 days after randomization. The study addresses the challenge that renal replacement therapy, while life-saving, may cause complications like hypotension and organ ischemia in these patients. Participants will be randomly assigned to receive either 20-25% albumin fluid or normal saline boluses during their renal replacement therapy sessions in the intensive care unit. Each treatment involves two 100 mL boluses one at the start and one halfway through each session. The renal replacement therapies include continuous renal replacement therapy CRRT, prolonged intermittent renal replacement therapy PIRRT, or intermittent hemodialysis IHD. Treatments will continue for up to 14 days in the ICU, with dosing schedules tailored to the type of renal replacement therapy. During the study, participants will be closely monitored for organ support-free days, renal replacement therapy-free days, and other health outcomes through 28 days, with extended follow-up for mortality and kidney function up to 365 days. Researchers will collect data on fluid balance, hypotension episodes during therapy, organ function scores, healthcare costs, and quality of life measures. The trial involves multiple intensive care units and includes comprehensive assessments to evaluate the impact and safety of albumin use in this critical condition.

This research aims to compare the effects of oral anticoagulation versus no anticoagulation in patients aged 55 and older who have had recent episodes of transient atrial fibrillation triggered by stress and have additional factors that increase their risk of stroke. The study is a multinational, investigator-initiated, prospective, randomized, open-label trial evaluating the impact of non-vitamin K oral anticoagulants NOACs on preventing stroke and other serious cardiovascular events. Participants will be randomly assigned to either receive one of several NOACs, such as edoxaban, apixaban, dabigatran, or rivaroxaban, prescribed by their physician for the duration of the follow-up, or to a control group that will not receive anticoagulants unless medically indicated during the study. The choice of specific NOAC and dose adjustments are determined by the prescribing doctor. The study excludes patients with certain conditions like chronic atrial fibrillation, severe kidney or liver disease, recent cardiac surgery, or bleeding risks. During the study, participants will be monitored for up to 24 months to assess the occurrence of non-hemorrhagic stroke, systemic embolism, vascular mortality, myocardial infarction, peripheral arterial thrombosis, amputation, and venous thromboembolism. Regular follow-up will include evaluation of these outcomes to measure the effectiveness and safety of anticoagulation compared to no anticoagulation. Participants will provide informed consent and remain under medical supervision throughout the trial.

Researchers are evaluating the effects of therapeutic-dose heparin compared to usual care pharmacological thromboprophylaxis in patients hospitalized with community-acquired pneumonia CAP. This international, open-label, randomized controlled trial aims to understand if higher doses of heparin can improve outcomes by addressing inflammatory and thrombotic processes that contribute to respiratory, cardiac, and organ complications in CAP. The study builds on findings from COVID-19 patients, where therapeutic-dose heparin showed benefits in non-critically ill patients. Participants are randomly assigned to one of two groups. One group receives a daily therapeutic dose of low molecular-weight heparin LMWH or unfractionated heparin UFH for up to 14 days or until hospital discharge. The other group receives usual care with thromboprophylactic dose anticoagulation following local protocols, with doses not exceeding half the therapeutic level. The investigational arm prefers LMWH but may use UFH, especially in cases of renal compromise, with dosing tailored to patient weight and local standards. During the study, participants will be monitored for survival over 30 days as the primary outcome. Secondary outcomes include bleeding events, heparin-induced thrombocytopenia HIT, thrombotic events, invasive mechanical ventilation, mortality at multiple time points, hospital-free days, and health-related quality of life. The study involves hospital assessments, close monitoring of safety and clinical status, and tracking of various health measures up to 180 days, ensuring comprehensive evaluation of the treatments under study.

Researchers are evaluating the effectiveness of two antiviral drugs, Paxlovid and Veklury, in preventing long-term cardiovascular problems following COVID-19 among hospitalized adults. This study, called the DEFEND trial, will be the first of its kind to focus on cardiovascular post-acute sequelae of SARS-CoV-2 in this patient group. It is a pilot, randomized, placebo-controlled trial designed to also help plan a larger future study by testing recruitment feasibility and accuracy of hospital outcome data. Participants will be randomly assigned to receive either Paxlovid orally twice daily for 5 days or Veklury intravenously once daily for 5 days, alongside standard care, or a matching placebo on the same schedule. The trial will enroll adults aged 18 or older who have tested positive for SARS-CoV-2 within 5 days of hospital admission and are not requiring supplemental oxygen. The study will recruit about 118 participants across four hospitals in Ontario, followed by a 12-month observation period after treatment. During the study, researchers will monitor participants from the time of screening through enrollment and track major cardiovascular events such as stroke, heart failure, venous thromboembolism, diabetes, or death within one year. They will also validate hospital data accuracy, assess reinfection, ICU admission, and drug safety within 90 days of the initial COVID-19 test. The trial includes thorough follow-up and safety monitoring over the full year to understand the long-term cardiovascular outcomes related to COVID-19 and the potential preventive effects of the antiviral treatments.

Researchers are evaluating ziltivekimab, a new medicine not yet approved anywhere, to see if it can help people who were hospitalized due to a heart attack. The study aims to find out if ziltivekimab can reduce the development of heart disease and prevent future heart attacks or strokes. This is a Phase 3 clinical trial comparing ziltivekimab to a placebo in patients with acute myocardial infarction. Participants will receive an initial loading dose of ziltivekimab or matching placebo by injection under the skin as soon as possible after an invasive heart procedure, within 36 hours for STEMI or 48 hours for NSTEMI patients. After the loading dose, they will get monthly injections of the same study medicine for up to two years, in addition to their standard care. During the study, participants will be monitored for major cardiovascular events such as heart attack, stroke, and cardiovascular death. Researchers will also track other heart-related outcomes and safety measures over a period of up to 25 months. The study involves regular visits for injections, assessments, and laboratory tests to evaluate the medicines effects and patient health throughout the trial.

This research evaluates common supportive care treatments used in intensive care units ICUs worldwide, focusing on vasopressors, platelet transfusions, and nutrition. It is an international, multi-center, randomized, adaptive platform trial studying how these interventions are used for critically ill patients, particularly those in states like cardiovascular shock or with thrombocytopenia. The study aims to improve the understanding of these therapies, which are widely used but not well supported by strong scientific evidence. Participants are assigned to different groups based on the intervention being studied. In the vasopressor domain, patients receive vasoactive medications with blood pressure targets set in four different ranges. The platelet domain randomizes ICU patients with low platelet counts to different thresholds for receiving platelet transfusions before procedures. The nutrition domain compares feeding patients either by boluses three times a day or continuous feeding over 24 hours. Each domain follows specific protocols to evaluate these approaches during ICU care. Throughout the study, participants undergo various assessments including monitoring mortality rates, organ dysfunction, bleeding outcomes, and quality of life. Data is collected at hospital discharge, up to 30 or 90 days, and for one year in some cases. The study measures include recruitment rates and clinical outcomes relevant to each domain. The trial will run from 2025 to 2030, with ongoing evaluations to guide supportive care in critical illness.

Researchers are evaluating how to best recommend chemotherapy for patients with Stage IIB, IIC, or Stage III colon cancer based on the presence or absence of circulating tumor DNA ctDNA after surgery. This Phase IIIII trial explores whether ctDNA status can help guide decisions about the need for adjuvant chemotherapy and identify the optimal chemotherapy regimen for those at high risk of recurrence. Circulating tumor DNA is a promising biomarker that may detect microscopic residual cancer cells that traditional methods might miss. Participants are assigned to groups based on their ctDNA results after surgery. Those without detectable ctDNA ctDNA- may undergo serial monitoring without treatment or receive different chemotherapy regimens such as mFOLFOX6 or CAPOX for 3 to 6 months. Patients with detectable ctDNA ctDNA who have a higher risk of recurrence are randomized to receive either standard chemotherapy regimens like mFOLFOX6 or CAPOX for 6 months or a more intensive regimen called mFOLFIRINOX for 6 months. Central ctDNA testing is performed using the Signatera test to guide these assignments. During the study, participants have blood samples collected for ctDNA testing and undergo imaging scans to check for cancer recurrence. Researchers assess disease-free survival, overall survival, and chemotherapy compliance over several years. The study includes monitoring for safety and treatment effects, with follow-up planned for up to 5 years after randomization. Participants health status, laboratory tests, and tumor markers are regularly evaluated throughout the treatment and follow-up periods.

This research focuses on patients undergoing noncardiac surgery to detect postoperative atrial fibrillation POAF, a condition linked to long-term health issues but often missed in routine care. The study aims to determine how often clinically important POAF occurs by using continuous heart monitoring after surgery. It is a multicenter prospective cohort study sponsored by the Population Health Research Institute. Participants will wear a portable cardiac monitoring device to continuously record their heart rhythm for up to 14 days, starting within 72 hours after their surgery. The monitoring period can last up to 14 days, and the study observes the incidence of POAF and related heart rhythm problems within 35 days of surgery. This approach seeks to improve detection compared to usual clinical monitoring. During the study, researchers will collect continuous ECG data, and participants will be followed to track heart rhythm events and any complications. The main measurement is the occurrence of clinically important POAF within 35 days after surgery. Secondary outcomes include other heart rhythm disturbances and death within the same period. The total participation time includes continuous monitoring and follow-up assessments within 35 days after surgery.

Researchers are investigating whether adding the drug Docetaxel to the usual hormone treatments, Androgen Deprivation Therapy ADT and Androgen-Receptor Pathway Inhibitor ARPI, can better control metastatic castration sensitive prostate cancer in men who have not responded optimally to initial hormone therapy. This phase III, international, open-label, randomized trial seeks to compare the effectiveness of this combined approach against the standard hormone therapy alone. Participants will be randomly assigned to receive either the standard hormone therapy with ADT plus ARPI or the same hormone therapy combined with Docetaxel chemotherapy. The trial focuses on men with metastatic prostate cancer who continue to have elevated PSA levels after 6 to 12 months of hormone-targeting treatment. Treatments are administered according to physician choice and assignment, and the study evaluates outcomes over a long period. During the trial, participants will be closely monitored with assessments including PSA levels and clinical progression over 39 months. Researchers will measure overall survival as the primary outcome, along with secondary outcomes such as PSA progression, PSA response, PSA kinetics, and progression-free survival. Participants must be accessible for treatment and follow-up to allow for complete documentation of treatment effects and adverse events throughout the study duration.