Laval

Researchers are evaluating the safety and effectiveness of combining durvalumab and domvanalimab compared to durvalumab plus placebo in adults with locally advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) whose disease has not worsened after definitive platinum-based concurrent chemoradiation therapy. This Phase III, randomized, double-blind, placebo-controlled, international study involves multiple centers. Participants receive intravenous infusions of durvalumab and domvanalimab or durvalumab and placebo. The treatments are given after patients have completed concurrent platinum-based chemotherapy and radiation therapy with a total radiation dose of approximately 60 Gy. The study monitors patients over time to assess treatment effects and safety. During the study, participants undergo evaluations including tumor tissue analysis for PD-L1 status, performance status assessments, and monitoring of organ and marrow function. The main outcome measured is progression-free survival up to 8 years after randomization. Researchers also monitor for any adverse effects and disease progression throughout the study period.

Researchers are investigating the effectiveness, safety, and tolerability of combining baxdrostat with dapagliflozin compared to dapagliflozin alone in people with chronic kidney disease (CKD) and high blood pressure. This Phase III, international, multicenter, double-blind, placebo-controlled study aims to see if this combination reduces risks such as significant kidney function decline, kidney failure, heart failure events, or cardiovascular death. The study includes a 4-week run-in period where participants not previously treated with SGLT2 inhibitors receive dapagliflozin alone. After this, participants are randomly assigned to receive either baxdrostat plus dapagliflozin or placebo plus dapagliflozin in a double-blinded manner. Study visits occur frequently initially (at 2, 4, 8, 16, 34, and 52 weeks after randomization) and then approximately every 4 months. If participants stop the blinded treatment early, they continue dapagliflozin alone unless specific criteria require its discontinuation. Participants will undergo regular assessments including blood pressure monitoring and laboratory tests related to kidney function and cardiovascular health. The primary outcome measures the reduction in risk of major kidney and heart events over up to 37 months. Even if participants stop the study treatment, they will continue follow-up visits and data collection to ensure comprehensive safety and efficacy evaluation throughout the study duration.

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 insulin icodec, a once-weekly insulin injection, compared to insulin glargine, a once-daily injection, in adults with type 1 diabetes. The study aims to see how well weekly insulin icodec controls blood sugar levels compared to daily insulin glargine when both are combined with insulin aspart. This phase 3 study will last about 26 weeks, or roughly 8.5 months. Participants will receive either insulin icodec or insulin glargine, both given as subcutaneous injections. All participants will also use insulin aspart as a subcutaneous injection. The study compares these two insulin regimens to assess their effects on blood sugar control over the 26-week period. During the study, researchers will monitor changes in glycosylated hemoglobin (HbA1c) from the start of the study to week 26. Participants will follow the study protocol including self-measured plasma glucose profiles. Safety and efficacy will be evaluated throughout the treatment period to understand the impact of the insulin regimens on blood sugar control and participant health.

Researchers are evaluating the effects of the drug orforglipron compared with a placebo on cardiovascular outcomes in adults who have atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). This is a Phase 3, randomized, double-blind, placebo-controlled study designed to investigate major adverse cardiovascular events over a long period. Participants will receive either orforglipron or a placebo orally. The study is event-driven and will continue until the occurrence of major cardiovascular events or up to about 5 years. The treatments are administered without revealing to participants which group they are in to ensure unbiased results. During the study, participants will be monitored for the time to the first occurrence of a major cardiovascular event. Researchers will collect data from baseline through the end of the study, which lasts approximately 5 years. Regular assessments will help evaluate the safety and effects of the treatments on cardiovascular health in this population.

Researchers are evaluating the effectiveness and safety of standard chemotherapy alone or combined with INCB161734 in participants who have metastatic pancreatic ductal adenocarcinoma (PDAC) with a KRAS G12D mutation. This phase 3, randomized, double-blind study focuses on individuals who have not received prior treatment for metastatic PDAC. The goal is to understand if adding INCB161734 to chemotherapy improves outcomes in this group of patients. Participants will receive either oral INCB161734 tablets or a placebo, along with a chemotherapy regimen selected by the investigator following specific protocol requirements. The chemotherapy options are defined by the study protocol. Treatments will be administered as planned during the study period, with careful monitoring to assess their effects. Throughout the study, participants will be monitored for overall survival up to approximately three years, progression-free survival, and objective tumor response assessed up to about two years. Researchers will conduct regular evaluations including clinical assessments and imaging reviewed by blinded independent central review (BICR). Safety and efficacy data will be collected to understand the impact of the treatments over time.

Researchers are evaluating the study medicine PF-08046054 compared to the standard chemotherapy drug docetaxel in adults with non-small cell lung cancer (NSCLC) that has spread or cannot be removed with surgery or radiation. Participants must have PD-L1 expression on 1% or more of their tumor cells and have experienced cancer progression during or after treatment with PD-L1 or PD-1 inhibitors, platinum-based chemotherapy, and targeted therapies for those with known genetic mutations. The trial is a Phase 3 randomized study to better understand how well PF-08046054 works alone compared to docetaxel alone. Participants will be randomly assigned to receive either PF-08046054 or docetaxel. Those in the PF-08046054 group will get intravenous (IV) infusions twice every 21-day cycle, while those in the docetaxel group will receive one IV infusion every 21 days. The treatment period may last up to 5 years if their NSCLC responds to the therapy. No other treatments are combined during the study period. Throughout the study, participants will have regular clinic visits for evaluations and monitoring to see how they respond to the treatment. Researchers will collect information on overall survival over approximately 5 years. They will also monitor safety and disease progression during these visits to understand the long-term effects and benefits of the treatments.

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 combination of cefazolin with ertapenem to improve treatment outcomes in adults with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. This phase 2 randomized controlled trial builds on existing laboratory, animal, and small human studies suggesting that adding ertapenem to cefazolin may shorten the duration of bacteremia and potentially reduce mortality, which remains high despite current treatments. The trial is a sub-study of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial. Participants will receive either adjunctive ertapenem or a saline placebo alongside standard cefazolin therapy. The study focuses on adults who have had S. aureus bacteremia diagnosed within the past 48 hours, with confirmed or likely MSSA infection. Up to 12-24 hours of other antibiotics such as vancomycin, linezolid, or daptomycin may be allowed initially if MRSA has not yet been excluded. Treatment duration and dosing details are managed according to clinical practice and study protocols. During the study, participants will be closely monitored for clinical success by day 5. Researchers will collect data on bacteremia duration, treatment response, and safety outcomes. Participants' clinical status, cultures, and any adverse events will be assessed regularly. The trial aims to provide important information on whether the cefazolin-ertapenem combination can improve recovery and reduce mortality in patients with MSSA bacteremia.

Atrial Fibrillation (AF) affects about 200,000 Canadians and raises the risk of stroke, illness, and death. A stroke can severely impact a person's ability to speak, eat, walk, work, care for themselves, and interact with others, and it can be fatal. AF causes slow blood flow in the heart's upper chambers, which can lead to blood clots that may travel to the brain and cause a stroke. Blood thinners, or anticoagulants, help reduce the chance of these clots forming and lower stroke risk by up to 95%. However, there has been no direct comparison between two newer blood thinners, rivaroxaban and apixaban, which are approved for stroke prevention in AF by Health Canada. This research compares the safety of taking apixaban twice daily versus rivaroxaban once daily in patients with non-valvular AF. Both drugs are taken by mouth and are direct oral anticoagulants (DOACs) that do not require regular blood tests or dietary restrictions like warfarin. The study is a phase 4 randomized controlled trial designed to assess the rate of bleeding events in patients using these medications over 12 months. Participants will be followed for one year, during which researchers will monitor for clinically relevant bleeding events, including major bleeding and other significant bleeding episodes. The study will collect information on safety and side effects to help guide the best choice of anticoagulant for patients with AF. This trial aims to provide important data to improve clinical decisions and patient care regarding stroke prevention in AF.