Worcester

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study. This trial focuses on patients with established atherosclerotic cardiovascular disease ASCVD or those at high risk for a first ASCVD event. The study aims to assess how AZD0780 compares to placebo in reducing the risk of major adverse cardiovascular events, also known as MACE-PLUS, over the course of the trial. Participants are randomly assigned to receive either oral AZD0780 once daily or a matching placebo once daily. The study continues until a primary analysis censoring date, which may be up to approximately 54 months from randomization. After this, a study closure visit will be conducted as the final visit for each participant. During the study, participants will be regularly monitored for cardiovascular events including heart attacks, strokes, urgent coronary revascularizations, and other related outcomes. Researchers will track the time to first occurrence of these events as the primary outcome. Safety and other secondary outcomes like all-cause mortality will also be assessed. The total participation time can last up to about 54 months, with ongoing evaluations throughout this period.

Researchers are evaluating the safety and effects of a new medicine called NNC0487-0111 in people who have Heart Failure with preserved Ejection Fraction HFpEF or Heart Failure with mildly reduced Ejection Fraction HFmrEF and excess body weight. This phase 3 clinical trial aims to find out if NNC0487-0111 is safe and effective for treating these conditions compared to a placebo. Participants have HFpEF or HFmrEF and a body mass index of 30 or above. The study is sponsored by Novo Nordisk AS and uses a randomized, quadruple-masked design. Participants will receive either NNC0487-0111 or a matching placebo by injection under the skin once a week. The NNC0487-0111 is given in increasing doses over time. The study is parallel in design, meaning participants are randomly assigned to one of the two groups and receive that treatment throughout the trial. This treatment period extends for up to about 165 weeks. The study evaluates the time to certain heart failure events, hospitalizations, cardiovascular deaths, and other major cardiovascular events. During the study, participants will be monitored regularly to assess heart failure outcomes and kidney function, as well as quality of life using questionnaires like the Kansas City Cardiomyopathy Questionnaire. Safety and effectiveness are assessed through hospital visits, heart failure event tracking, and blood tests including kidney function and blood sugar levels. The total participation spans over three years, with ongoing evaluations to measure the time to heart failure events and cardiovascular outcomes. Participants receive close medical monitoring throughout the study period.

Researchers are evaluating the addition of Tersolisib LY4064809STX-478 to other anti-cancer drugs as a first treatment for adults with advanced hormone receptor-positive HRhuman epidermal growth factor receptor 2-negative HER2- breast cancer that has a PIK3CA mutation. This Phase 3 randomized, double-blind, placebo-controlled trial aims to understand the efficacy and safety of this combination compared to placebo, focusing on improving outcomes for patients with this specific genetic change. Participants receive LY4064809 orally in one of two doses combined with a CDK46 inhibitor such as Ribociclib, Palbociclib, or Abemaciclib and endocrine therapy ET administered orally or via intramuscular injection. The comparison group receives a placebo combined with the same CDK46 inhibitor and ET. The study includes two parts Part 1 explores dose optimization, and Part 2 evaluates the treatment combinations effectiveness and safety as a first-line therapy. During the study, participants will have regular assessments to monitor cancer response, progression, and safety over an estimated period of up to 5 years or more. Researchers will measure outcomes such as overall response rate, progression-free survival, duration of response, overall survival, and quality of life. Treatment continues as long as the cancer benefits without intolerable side effects. Safety monitoring, laboratory tests, and quality of life questionnaires are part of the participant involvement throughout the trial.

Researchers are evaluating two types of stereotactic body radiotherapy SBRT in men with high risk localized prostate cancer, where the cancer is confined to the prostate but may grow quickly or spread. The study aims to compare the safety and effectiveness of delivering radiotherapy to the prostate alone versus the prostate plus surrounding lymph nodes, with both treatments given in only 5 sessions. This phase III trial is designed to see if including lymph nodes reduces the chance of cancer returning and to review any side effects that occur. Participants will be randomly assigned to one of two groups. One group will receive SBRT targeting the prostate and seminal vesicles, delivering 36.25Gy in 5 fractions on alternate days with 40Gy to the prostate clinical target volume. The other group will get the same prostate treatment plus 25Gy in 5 fractions to the pelvic lymph nodes on alternate days. Treatments will be provided over approximately two weeks at experienced NHS radiotherapy centers that meet quality standards for these therapies. During the study, participants will be monitored for at least three and a half years to assess time to biochemical or clinical failure, which is the main outcome. Researchers will also track acute and late side effects, cancer relapse, survival rates, patient-reported outcomes, and adherence to treatment protocols for up to five years post-randomization. Regular imaging and assessments will be performed before treatment to confirm eligibility and exclude metastatic disease. Overall, participants can expect close monitoring and follow-up throughout and after their treatment period.

Researchers are evaluating the acceptability, gastrointestinal tolerance, and compliance of a bolus tube feed with food blends for children and adults who require enteral feeding due to conditions such as short bowel syndrome, inflammatory bowel disease, total gastrectomy, dysphagia, bowel fistulae, feeding intolerances, developmental disabilities, and disease-related malnutrition. This prospective study aims to collect data on how well patients tolerate and adhere to this dietary management over 28 days. Participants will use the bolus tube feed alongside their usual tube feed or homemade blended diet. The study involves a 7-day period of monitoring gastrointestinal tolerance and a 28-day period of recording formula intake. Each participant acts as their own control, and the study will include up to 50 children and adults who are gastrostomy fed and stable on their current feeding regimen. During the study, participants will be assessed for gastrointestinal tolerance over one week and will keep daily records of formula intake for four weeks. At the end of the study, a patient satisfaction questionnaire will be completed to gather feedback. Researchers will monitor adherence and collect data to evaluate the formulas acceptability and tolerance in the target population.

Researchers are evaluating the use of EEG-based Brain-Computer Interface BCI technology to detect awareness and enable communication in people with prolonged disorders of consciousness DoC, such as unresponsive wakefulness syndrome UWS, minimally conscious state MCS, and locked-in syndrome LIS. The study aims to improve diagnosis accuracy where traditional methods relying on motor responses may fail, and to explore if BCI can provide movement-independent communication. The trial also investigates whether training with BCI can enhance brain response consistency and communication ability. Participants undergo three phases Phase I assesses if patients can imagine movements and produce detectable brain activity using EEG. Phase II involves training with motor imagery BCI and real-time auditory feedback to help participants modulate brain signals. Phase III tests participants ability to answer yes-no questions using imagined movement patterns. The study uses specific imagined movement combinations to represent yes or no responses, tailored individually and applied throughout sessions lasting about 1.5 hours each. During the study, participants complete up to 10 sessions including assessments, training, and communication tasks. Researchers monitor changes in BCI performance accuracy, ability to communicate consistently, and clinical scale scores related to consciousness and recovery. The study evaluates how feedback types and timing affect performance and collects data to support clinical diagnosis and potential therapeutic benefits. Participation involves EEG recordings, neurofeedback, and answering structured questions over several weeks.

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.

Researchers are studying maridebart cafraglutide to evaluate its effect on reducing cardiovascular problems and death in people with atherosclerotic cardiovascular disease who are also overweight or obese. This Phase 3 trial compares maridebart cafraglutide to a placebo, both given alongside standard care, to see if maridebart cafraglutide works better in lowering heart-related risks. Participants will receive either maridebart cafraglutide or a placebo, both administered by subcutaneous injection. The study lasts for up to approximately 35 months, during which researchers monitor several heart and health outcomes. These include heart attacks, strokes, death rates, hospitalizations, blood pressure, body measurements, blood sugar control, cholesterol levels, kidney function, and inflammatory markers. During the trial, participants will have regular assessments including physical exams, blood tests, and monitoring of heart events. Researchers track the time to first major heart-related events and changes in health markers over the study period. Safety is also monitored by recording any adverse events. The total participation time can last nearly three years, allowing careful observation of the effects of the study drug compared to placebo.

Researchers are evaluating two strategies for complete revascularization in patients with acute myocardial infarction MI specifically ST-segment elevation MI STEMI or non-ST-segment elevation MI NSTEMI who also have multivessel coronary artery disease CAD and have undergone successful treatment of the culprit lesion with Percutaneous Coronary Intervention PCI. The study aims to compare physiology-guided complete revascularization to angiography-guided complete revascularization, focusing on both efficacy and safety outcomes. Participants are randomly assigned to one of two groups. One group receives physiology-guided PCI where the function of non-culprit lesions NCLs is assessed using resting full-cycle ratio RFR or fractional flow reserve FFR, with PCI performed on lesions meeting specific thresholds. The other group undergoes angiography-guided PCI, receiving routine staged PCI on all qualifying NCLs identified before randomization. Both approaches follow local practice standards for PCI. During the study, researchers monitor participants for a minimum of two years to assess the time to first occurrence of major cardiovascular events, including cardiovascular death, new MI, or ischemia-driven revascularization, as well as safety outcomes like significant bleeding, stroke, stent thrombosis, or kidney injury related to contrast use. The trial also includes an observational imaging study using optical coherence tomography in a subset of patients. Follow-up assessments will enable evaluation of both efficacy and safety over the study period.

Researchers are studying breast cancer patients who have Triple Negative Breast Cancer TNBC andor a germline BRCA mutation gBRCA to see if adding olaparib, a PARP enzyme inhibitor, to platinum-based neoadjuvant chemotherapy is safe and improves the complete response rate at surgery. This is a randomized, open-label phase IIIII trial conducted in three stages, involving at least 780 patients, including 220 with gBRCA mutations. Participants receive at least 21 weeks of chemotherapy before surgery. Study groups include a control arm receiving paclitaxel and carboplatin, and two experimental arms where patients receive the same chemotherapy plus oral olaparib tablets taken twice daily during specified days of each 3-week cycle. Additional treatments such as prophylactic granulocyte-colony stimulating factor and anthracyclines are given as per local practice. Patients with residual disease after chemotherapy may join a sub-study with further treatments. During the trial, patients undergo screening tests including BRCA mutation testing, tumor marker assessments, and standard cancer staging. Researchers monitor treatment safety and effectiveness through pathological complete response rates, adverse events, survival outcomes, quality of life questionnaires, and imaging. Follow-up occurs for up to 10 years after surgery, with safety data regularly reviewed by independent committees to ensure participant well-being.