Alkmaar

Researchers are evaluating the efficacy and safety of rilvegostomig compared to pembrolizumab, both combined with platinum-based doublet chemotherapy, as a first-line treatment for patients with locally advanced or metastatic non-squamous non-small cell lung cancer NSCLC whose tumors express PD-L1 at levels of 1% or higher. This Phase III, randomized, double-blind, global study aims to compare these treatments to improve outcomes for this patient group. Participants will receive either rilvegostomig or pembrolizumab, each given intravenously on Day 1 of every 21-day cycle, combined with platinum-based doublet chemotherapy either carboplatin or cisplatin also given on Day 1 of each cycle for up to four cycles. After chemotherapy cycles, patients continue with rilvegostomig or pembrolizumab monotherapy combined with pemetrexed maintenance. The study follows patients for up to approximately six years to monitor treatment effects and safety. During the study, participants undergo assessments including imaging scans to measure tumor size, blood tests to evaluate organ function, and questionnaires about symptoms and quality of life. Researchers monitor overall survival and progression-free survival as primary outcomes, alongside other measures such as response duration and physical functioning. Safety is closely observed throughout, with study visits scheduled regularly during treatment and follow-up periods, lasting up to six years in total.

Researchers are evaluating the safety and effectiveness of rilvegostomig combined with platinum-based chemotherapy compared to pembrolizumab combined with platinum-based chemotherapy as a first treatment for patients with locally advanced or metastatic squamous non-small cell lung cancer mNSCLC whose tumors express programmed death-ligand 1 PD-L1. This Phase III global study focuses on patients with PD-L1 tumor cell expression of 1% or higher and aims to determine which treatment provides better overall and progression-free survival. Participants will be randomly assigned to one of two study groups one group will receive rilvegostomig plus carboplatin and either paclitaxel or nab-paclitaxel chemotherapy, while the other group will receive pembrolizumab plus the same chemotherapy options. Rilvegostomig and pembrolizumab are both given intravenously on Day 1 of each 21-day cycle, with chemotherapy given up to 4 cycles. Nab-paclitaxel may be administered on Days 1, 8, and 15 of each cycle. Treatment continues with rilvegostomig or pembrolizumab until disease progression or other criteria are met. During the study, participants will undergo regular assessments including imaging scans to measure tumor response, laboratory tests to monitor organ function, and patient questionnaires about physical function and quality of life. Researchers will track overall survival, progression-free survival, response rates, and duration of response for up to approximately 6 years. Safety and immune response to rilvegostomig will also be evaluated. Participants will be closely monitored throughout the treatment and follow-up periods.

Researchers are evaluating a person-centered multicomponent intervention program to prevent and reduce agitation and the use of physical restraints in adult patients in intensive care units ICUs. This program combines non-drug approaches with light sedation guided by the drug dexmedetomidine. The study aims to compare this approach with the usual care that includes physical restraints, focusing on both short- and long-term patient outcomes and healthcare costs. The study involves two groups one receiving the multicomponent intervention program, which uses non-pharmacological methods combined with goal-directed light sedation using dexmedetomidine when needed, and the other receiving standard care that may include physical restraints. The intervention is designed for adult ICU patients who are agitated or expected to become agitated during their ICU stay. Participants will be monitored for various outcomes including ICU-free days within 28 days, rates of device removal, reintubations, days with delirium or coma, use of physical restraints and sedative drugs, duration of mechanical ventilation, hospital stay length, mortality at multiple time points, as well as physical, mental, cognitive outcomes and quality of life up to 24 months. Safety and cost-effectiveness will also be evaluated. The total follow-up may extend up to one year or more, with detailed assessments at several time points.

This study evaluates the long-term safety and tolerability of pelacarsen TQJ230 in people with established cardiovascular disease and elevated Lipoproteina who completed a previous related study. It is an open-label extension trial, meaning all participants receive the study drug without placebo comparison. The trial is sponsored by Novartis Pharmaceuticals and focuses on continued treatment after the completion of the parent study. Participants receive monthly injections of pelacarsen 80 mg subcutaneously for up to 36 months during this extension phase. This phase is designed to provide access to the study drug after the initial trial and to monitor participants closely. The study does not involve randomization or blinding, and all enrolled participants receive the active drug. During the study, participants will undergo regular assessments including monitoring for adverse events and cardiovascular events, as well as measuring Lipoproteina levels at baseline and several time points over 36 months. Safety and tolerability will be closely tracked throughout the treatment period. The total duration of participation corresponds to the length of the extension phase, up to three years.

This research aims to evaluate whether preventive endovascular stenting of a significant narrowing over 50% in the superior mesenteric artery SMA can reduce the risk of anastomotic leakage AL after elective colon surgery. AL is a serious complication linked to higher mortality, lower quality of life, and increased healthcare costs. A prior study showed that having more than 50% SMA stenosis raises the risk of AL sixfold, and this trial investigates if stenting this artery before surgery can help prevent AL. Participants are randomly assigned to one of two groups the intervention group will receive preventive angioplasty and placement of a covered stent in the SMA before their colon surgery, while the control group will proceed with colon surgery without stenting. Both groups receive daily mono antiplatelet therapy with carbasalate calcium, lifelong for the intervention group and at least 12 months for the control group. The stenting procedure is minimally invasive and performed preferably within two weeks before surgery at specialized centers. Colon surgery is done according to standard local guidelines. Some centers will use intraoperative fluorescence angiography to assess blood flow during surgery. During the 12 months of follow-up after surgery, participants will be monitored for anastomotic leakage within the first 90 days, as well as delayed leakage and surgical complications up to one year. Researchers will collect data on hospital stays, reinterventions, mortality, quality of life, healthcare costs, and stent function. Patient-reported outcomes will be gathered through questionnaires at multiple time points. The study also includes imaging assessments and cost-effectiveness analyses to understand the broader impact of preventive stenting.

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 a shorter treatment duration with androgen receptor pathway inhibitors ARPIs, specifically Apalutamide or Enzalutamide, in patients with low-volume hormone-sensitive metastatic prostate cancer. This phase 3 clinical trial aims to determine if stopping ARPI therapy after 12 months, with the option to restart if the cancer progresses, is not worse than continuing ARPI treatment. The goal is to reduce side effects and costs while maintaining effective disease control. Participants will be randomly assigned after completing 12 months of ARPI treatment to one of two groups one group will continue androgen deprivation therapy ADT combined with ARPI, while the other will stop ARPI after 12 months but may restart it if a confirmed rise in prostate-specific antigen PSA occurs. The PSA confirmation sample must be taken at least four weeks after the initial rise. Treatment will be monitored closely according to these protocols. During the study, participants will be followed for up to 6 years, including 5 years after randomization to track clinical progression-free survival. Researchers will regularly assess disease status, treatment effects, and possible side effects. The study includes regular visits and monitoring to evaluate how long patients remain free from disease progression while comparing the two treatment approaches.

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.

Researchers are evaluating the effect of muvalaplin in lowering cardiovascular risks among adults with elevated lipoproteina who either have atherosclerotic cardiovascular disease or are at risk of a first heart attack or stroke. This phase 3, randomized, double-blind study aims to investigate whether muvalaplin can reduce major adverse cardiovascular events compared to placebo in this high-risk population. Participants are randomly assigned to receive either muvalaplin or a placebo, both given orally. The study is designed with parallel groups and will last about 5.25 years, during which the occurrence of cardiovascular events and changes in lipoproteina levels will be closely monitored. Throughout the study, participants will undergo regular assessments including measurement of lipoproteina levels, monitoring of cardiovascular events such as heart attacks or strokes, and evaluation of healthcare resource use. The primary outcome is the time to first major adverse cardiac event, tracked from baseline until the study ends. Safety and pharmacokinetics of muvalaplin will also be evaluated during the trial period.

Researchers are studying patients with non-metastatic stage II colon cancer who are part of the Dutch ColoRectal Cancer cohort PLCRC and who consented to additional blood samples. The study aims to evaluate how many patients with detectable circulating tumor DNA ctDNA after surgery begin adjuvant chemotherapy. This observational and interventional trial includes patients who do not have a standard indication for chemotherapy and involves a randomized design to compare ctDNA-guided treatment with standard care. Patients are randomly assigned to one of two groups the ctDNA-based treatment group or the standard care group. In the ctDNA group, blood samples taken after surgery are analyzed for ctDNA. Those with detectable ctDNA are offered 3 months of adjuvant chemotherapy using CAPOX a combination of fluoropyrimidine and oxaliplatin. Patients without detectable ctDNA receive routine follow-up care. The standard care group receives routine follow-up without knowledge of their ctDNA results. Participants will have blood collected before surgery, after surgery, and during follow-up. Researchers will monitor who starts chemotherapy within 8 to 12 weeks after surgery and will track recurrence rates, disease-free survival, overall survival, time to recurrence, quality of life, and cost-effectiveness over several years. Follow-up assessments occur up to 10 years, allowing detailed long-term evaluation of treatment impact and patient outcomes.