York

Researchers are evaluating two different pacing methods for patients with slow heart rates, called bradycardia. This study compares the common right ventricular pacing approach with a newer physiological pacing method that includes His bundle and left bundle area pacing. The trial aims to better understand how these pacing techniques affect patient outcomes, including mortality and heart failure morbidity, in a large group of 2600 patients. Participants will receive a pacemaker implant and be randomly assigned to either right ventricular pacing or physiological pacing. The physiological pacing may involve His bundle pacing or left bundle pacing, but if these are not successful, biventricular pacing will be used. A subgroup of 500 participants will take part in an optional echocardiographic sub-study to assess heart function changes over a 24-month period. Throughout the study, patients will be assessed at baseline and every six months after randomization, with follow-up lasting up to 78 months. Researchers will monitor outcomes such as mortality, heart failure events, device-related safety issues, patient quality of life, symptoms, and pacemaker-derived data like arrhythmias and activity levels. The echocardiographic sub-study will measure specific heart function changes to understand pacing-induced cardiomyopathy. Participants involvement includes implantation, regular follow-up visits, questionnaires, and optional imaging assessments.

Researchers are evaluating whether retatrutide and tirzepatide can prevent major adverse liver outcomes in adults with metabolic dysfunction-associated steatotic liver disease MASLD who are at high risk based on non-invasive tests. This Phase 3 randomized controlled trial aims to assess these treatments compared to placebo in about 4,500 adults over approximately 224 weeks. The study is sponsored by Eli Lilly and Company and focuses on liver disease progression and related health measures. Participants will be randomly assigned to receive retatrutide, tirzepatide, or placebo, all administered by subcutaneous injection. The trial includes two placebo groups corresponding to each experimental drug. After completing the main study, eligible participants may join a 2-year extension where all will receive either retatrutide or tirzepatide regardless of their initial assignment. During the study, participants may attend around 25 to 30 clinic visits for health monitoring, study procedures, and assessments of liver function and disease status. Researchers will measure the time to major adverse liver outcomes, changes in liver fibrosis scores, liver stiffness, liver fat content, liver enzyme levels, body weight, and cardiovascular events. Monitoring will continue from baseline through study completion, with detailed evaluations at multiple timepoints including week 104.

Researchers are evaluating the efficacy and safety of two different dose regimens of pegozafermin compared to a placebo in adults with metabolic dysfunction-associated steatohepatitis MASH who have liver fibrosis stage F2 or F3. This Phase 3 study aims to better understand how pegozafermin may impact liver fibrosis and steatohepatitis in this population. Participants will receive subcutaneous injections of either one of two pegozafermin regimens or a matched placebo. These treatments are given in parallel groups, and participants are randomly assigned to one of the study groups. The study compares the effects of pegozafermin on liver fibrosis and steatohepatitis over a treatment period that includes evaluations up to 52 weeks and monitoring for disease progression up to 5 years. During the study, participants will be monitored through biopsies and blood tests to assess liver fibrosis improvement, resolution of steatohepatitis, changes in liver enzyme levels, and enhanced liver fibrosis scores. Safety and disease progression are also tracked throughout the study period. The total participation duration includes treatment and long-term observation to evaluate outcomes and any potential changes in liver health.

Researchers are evaluating the experimental drugs pozelimab and cemdisiran for treating Geographic Atrophy GA, a late stage of Age-related Macular Degeneration AMD that affects central vision. The study aims to compare the progression rate of GA in patients receiving cemdisiran alone, the combination of pozelimab and cemdisiran, or a placebo. Additional goals include monitoring side effects, drug levels in the blood over time, and the bodys antibody response to these drugs. Participants will receive subcutaneous injections of either pozelimab combined with cemdisiran, cemdisiran alone, or a placebo. The study is randomized and double-masked with three groups receiving different treatments. Treatment and monitoring will continue through specified time points up to 104 weeks, with follow-up on safety and antibody responses extending even further. During the study, participants will attend regular clinic visits for eye exams, imaging using Fundus Autofluorescence to measure GA lesion growth, vision tests including visual acuity and contrast sensitivity, and blood tests to assess drug levels and antibody formation. Researchers will track treatment-emergent adverse events and evaluate changes in vision and GA progression over time. Participation lasts until the study completion date in April 2033, with primary outcomes assessed at 52 weeks and further evaluations up to 296 weeks.

Researchers are evaluating the efficacy and safety of trontinemab in people with early symptomatic Alzheimers disease, ranging from mild cognitive impairment to mild dementia due to Alzheimers. This Phase III study aims to better understand the impact of trontinemab on cognitive decline and daily functioning in this population. The study is randomized, double-blind, and placebo-controlled to ensure reliable results. Participants will be assigned to receive either intravenous trontinemab or an intravenous placebo. The treatment period lasts up to 72 weeks, during which participants receive infusions as scheduled. Assessments include brain imaging such as amyloid and tau PET scans, cerebrospinal fluid and blood biomarker collection, and cognitive testing. The study also monitors safety through tracking adverse events, infusion-related reactions, and anti-drug antibodies. Participants will attend visits for evaluations including clinical dementia rating, cognitive scales like MMSE and ADAS-Cog-13, and daily living activities assessments. Safety monitoring involves MRI scans and lab tests. The primary outcome measured is the change in Clinical Dementia Rating, Sum of Boxes CDR-SB, from baseline to Week 72. The total duration of participation extends through the 72-week treatment and assessment period, with ongoing safety evaluations.

Researchers are evaluating the effectiveness, safety, and tolerability of a vaccine designed to reduce Clostridioides difficile C. difficile infections in adults aged 65 years and older. This phase 3 study compares the vaccine to a placebo in a group of older adults who have recent or planned contact with healthcare systems or recent antibiotic use. The purpose is to understand how well the vaccine works to prevent infections and to monitor any side effects or reactions. Participants will receive either the C. difficile vaccine or a placebo shot injected into the upper arm muscle. The study is randomized, double-blinded, and placebo-controlled. The vaccination period includes two doses and participants will be monitored for up to about three and a half years. Follow-up includes three planned clinical visits and three phone visits initially, then yearly clinic visits until the study ends. Participants are asked to report and save stool samples if they experience three or more loose stools in 24 hours to check for possible infection. During the study, researchers will track local and systemic reactions to the vaccine within seven days after each shot, adverse events up to one month after each vaccination, and serious adverse events for up to 18 months after the last dose. The main measurement is the occurrence of medically attended primary C. difficile infections from two weeks after the second vaccination through the surveillance period. Safety monitoring and annual visits will continue until the study is completed, which could be sooner or later depending on infection rates.

Researchers are evaluating the use of rimegepant for intermittent prevention of menstrual migraine in women aged 18 to 45 who experience migraine attacks related to their menstrual cycle. This Phase 3, double-blind, randomized study compares rimegepant with placebo to assess its efficacy and safety during the peri-menstrual period. The study focuses on migraine frequency and severity in women with a history of menstrual migraine and regular menstrual cycles. Participants receive either rimegepant 75 mg orally disintegrating tablets for 7 days during each peri-menstrual period or a matching placebo, along with standard care for acute migraine treatment as needed. The study treatment cycles are repeated over 5 menstrual cycles in the double-blind treatment phase. The study also includes an acute treatment dosing option with rimegepant as needed. During the study, participants will be monitored for changes in the number of migraine and headache days, use of migraine medications, and functional disability related to migraine. Cognitive function is also assessed. Researchers will conduct evaluations over 5 months, covering 5 menstrual cycles, and measure outcomes related to migraine frequency and severity during the peri-menstrual period. Safety and tolerability will be closely monitored throughout the study.

Researchers are evaluating whether the combination of vicadrostat BI 690517 and empagliflozin helps adults with heart failure who have symptoms and a left ventricular ejection fraction LVEF of 40% or more. This phase III study is designed to compare the effects of vicadrostatempagliflozin tablets versus placeboempagliflozin tablets on heart failure outcomes. The study aims to understand if this combined treatment improves health and reduces heart-related events. Participants are randomly assigned to one of two groups one group takes vicadrostat plus empagliflozin tablets once a day, and the other takes placebo plus empagliflozin tablets once a day. The study has no fixed duration and continues as long as participants benefit and tolerate the treatment. Throughout the study, participants visit their doctors regularly for health checks, and study staff may also contact them by phone to monitor well-being and any side effects. During the study, researchers monitor participants health through regular doctor visits and phone contacts. They collect data on heart-related events such as cardiovascular death, hospitalizations for heart failure, and urgent visits for heart failure over up to 42 months. Participants also answer questions about their symptoms and well-being. The study carefully tracks safety and treatment tolerance while gathering information to determine if the combined treatment helps people with heart failure.

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 evaluating whether skipping additional axillary treatment for patients with early-stage breast cancer who had cancer in their lymph nodes before chemotherapy but show no remaining cancer in those nodes after treatment is as effective as the standard approach. This study focuses on disease-free survival and reducing the risk of lymphoedema five years after treatment. It is a randomized, open, multicenter trial including patients with specific breast cancer stages and confirmed nodal metastases. Participants will all receive standard therapies including HER2-targeted treatment, endocrine therapy, and radiotherapy to the breast or chest wall if needed. They will be randomly assigned to one of two groups one group will not get further axillary treatment such as lymph node removal or radiotherapy, while the other group will receive these axillary treatments according to local guidelines. Follow-up visits will occur annually for at least five years. During the study, participants will undergo assessments to monitor disease-free survival and self-reported lymphoedema using specific questionnaires. Additional evaluations include arm function, quality of life, recurrence rates, survival, and cost-effectiveness analyses. The total study duration is planned for 120 months, including setup, recruitment, follow-up, analysis, and reporting.