Worcester

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study to see if it can reduce the risk of major adverse cardiovascular events (MACE-PLUS) in adults with established atherosclerotic cardiovascular disease (ASCVD) or those at high risk for a first ASCVD event. The study compares AZD0780 to a placebo and monitors participants from randomization until the primary analysis censoring date, followed by a final study closure visit. Participants will be randomly assigned to receive either oral AZD0780 or an oral placebo once daily. The treatment period lasts until the primary analysis censoring date, after which a study closure visit will occur. The study is event-driven and designed to assess the time to the first major cardiovascular event during treatment. During the study, participants will be closely monitored with various assessments to evaluate cardiovascular outcomes and safety over approximately 54 months. Researchers will track the time to first event of any component of MACE-PLUS and collect data to assess the effect of AZD0780 compared to placebo. The study includes regular visits and evaluations to ensure participant safety and adherence to treatment.

Researchers are evaluating the effectiveness and safety of adding Tersolisib (LY4064809/STX-478) to other anti-cancer drugs as the first treatment for adults with advanced hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This phase 3 study focuses on participants whose cancer has a specific genetic change called a PIK3CA mutation and who have not received prior treatment for advanced breast cancer. The study aims to understand how well this treatment combination works and its safety over time. Participants will receive Tersolisib or a placebo, combined with a CDK4/6 inhibitor (Ribociclib, Palbociclib, or Abemaciclib) and endocrine therapy (Anastrozole, Letrozole, Exemestane, or Fulvestrant). All drugs are given orally except for Fulvestrant, which is given by injection into the muscle. The study includes two parts: Part 1 allows participants who have had up to two prior treatments for advanced breast cancer, including chemotherapy; Part 2 includes those with no prior treatment for advanced disease and classifies them as endocrine sensitive or resistant based on their cancer history. During the study, participants will be regularly assessed for cancer response, progression-free survival, and side effects. Researchers will monitor measurable disease or bone involvement and track overall response rates, including complete or partial tumor shrinkage. The study will continue as long as the treatment is helping without causing unbearable side effects. Follow-up may last up to five years to observe long-term outcomes and safety.

Researchers are evaluating the safety and effectiveness of advanced external beam radiotherapy called stereotactic body radiotherapy (SBRT) in men with high risk localized prostate cancer. This cancer is limited to the prostate but has a high chance of growing quickly or spreading. The study compares SBRT given to the prostate alone versus SBRT given to both the prostate and surrounding lymph nodes. It is a Phase III trial involving 1128 participants to see which treatment option is better and safer over at least three and a half years of follow-up. Participants receive radiotherapy in 5 visits over two weeks. Half of the men will have SBRT targeted only to the prostate, while the other half will have it directed to both the prostate and pelvic lymph nodes. The treatments are delivered at NHS radiotherapy centers experienced with SBRT and pelvic node radiotherapy. Quality assurance ensures the treatments are administered properly. During the study, men will undergo scans including multi-parametric MRI and various types of PET-CT or MRI to stage their cancer before treatment. Researchers will monitor side effects and cancer outcomes to assess safety and effectiveness. The main outcome measured is the time until biochemical or clinical failure, with a minimum follow-up of 3.5 years after randomization. Participants will be closely followed for side effects and cancer control throughout the study period.

Researchers are evaluating the acceptability, gastrointestinal tolerance, and compliance of a bolus tube feeding formula blended with food in both children and adults over a 28-day period. This study focuses on patients requiring dietary management for conditions such as short bowel syndrome, intractable malabsorption, inflammatory bowel disease, total gastrectomy, dysphagia, bowel fistulae, feeding intolerances, developmental disabilities, and disease-related malnutrition. Up to 50 participants with cerebral palsy or oncology conditions will be included. Participants will receive the bolus tube feed alongside their usual tube feed or home-made blended diet. The study will monitor gastrointestinal tolerance during the first 7 days and track formula intake daily throughout the 28-day study period. The bolus tube feed is given via gastrostomy tube, and doses and duration of intake will be recorded. At the end of the study, participants will complete a patient satisfaction questionnaire to assess their experience with the tube feed. During the study, researchers will collect data on gastrointestinal symptoms, formula intake, and participant satisfaction. Compliance with the feeding regimen will be monitored, and safety will be assessed through regular observations. The total study duration for each participant is 28 days, during which intake and tolerance are carefully recorded to understand how well the bolus tube feed is accepted and tolerated in this patient population.

Researchers are investigating the use of EEG-based Brain-Computer Interface (BCI) technology to detect awareness and enable communication in individuals with disorders of consciousness, including unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS), and locked-in syndrome (LIS). The study explores whether these patients can imagine movements and use brain activity patterns to communicate, aiming to improve diagnostic accuracy and provide alternative communication methods for those unable to produce consistent motor responses. Participants undergo a three-phase study involving EEG-based BCI assessments and training. Phase I (sessions 1-2) evaluates the ability to imagine movements and produce detectable brain activity. Phase II (sessions 3-6) involves motor imagery BCI training with neurofeedback to help participants learn to modulate brain activity. Phase III (sessions 7-10) assesses the ability to use imagined movements to answer yes/no questions across various categories such as biographical and situational awareness. The BCI system uses combinations of imagined movements (left arm, right arm, feet) to represent answers. During the study, participants complete about 10 sessions of approximately 1.5 hours each, involving training and assessment tasks. Researchers monitor changes in performance accuracy using the BCI before and after training and evaluate the ability to consistently communicate yes/no responses over multiple sessions. Assessments include brain activity recordings, neurofeedback, and responses to structured questions. The study also examines how BCI technology may complement clinical assessments and potentially offer therapeutic benefits.

Researchers are evaluating whether avoiding further axillary treatment after neoadjuvant chemotherapy (NACT) is as effective as standard axillary treatment for patients with early stage breast cancer who initially had cancer in the lymph nodes confirmed by needle biopsy but show no residual cancer in the lymph nodes after NACT. The study aims to determine if skipping axillary lymph node dissection (ALND) or axillary radiotherapy (ART) affects disease free survival (DFS) and whether it reduces the risk of lymphoedema five years after treatment. This phase 3, open-label, randomized trial includes patients with T1-3N1M0 breast cancer and confirmed nodal metastases who have undergone sentinel node biopsy removing at least three lymph nodes post-NACT.

Researchers are evaluating maridebart cafraglutide, a drug given as an addition to standard care, to see if it reduces heart-related problems and deaths better than a placebo in people with atherosclerotic cardiovascular disease who are overweight or obese. This phase 3 study focuses on cardiovascular events such as heart attacks, strokes, and deaths related to heart conditions, aiming to improve outcomes in this high-risk population. Participants will receive either maridebart cafraglutide or a placebo, both administered by injection under the skin. The study compares these two groups over a period of up to approximately 35 months, monitoring heart-related health events to assess the drug's impact. The placebo group will receive injections that look identical but contain no active drug, ensuring a double-blind study design. During the study, participants will be regularly evaluated for major cardiovascular events, including heart attack, stroke, heart failure, and death. Researchers will track the time until these events occur to measure the drug's effectiveness. Safety and health will be closely monitored throughout the study period, and participants will be followed for up to nearly three years to gather comprehensive data on cardiovascular outcomes and overall survival.

Migraine is a neurological condition causing moderate to severe headaches often accompanied by nausea, vomiting, and sensitivity to light and sound. This research aims to assess how well atogepant works in adults with migraine when used in everyday medical practice. Atogepant is an approved preventive treatment for migraines, and the study will include about 1000 adult participants prescribed this medication by their doctors worldwide. Participants will take atogepant tablets orally as prescribed by their healthcare providers following usual medical care. The study will observe participants over a two-year period without requiring extra treatments or procedures beyond their regular clinical visits. These visits will occur at hospitals or clinics according to each participant's routine care schedule. During the study, participants will attend regular check-ups where researchers will monitor their health and migraine symptoms. The main outcome measured will be the percentage of participants who report feeling "much better" or "very much better" by week 12, based on their own impression of change. There are no additional burdens expected for participants beyond their normal treatment and follow-up appointments.

Researchers are evaluating two strategies for complete revascularization in patients with acute myocardial infarction (MI), including both ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI), who also have multivessel coronary artery disease (CAD). The trial compares physiology-guided revascularization, which uses specific measurements to decide treatment, with angiography-guided revascularization, which relies on imaging. The study aims to determine if the physiology-guided approach is not worse than the angiography-guided method in preventing cardiovascular death, new MI, or ischemia-driven revascularization, and whether it is better at reducing safety issues like bleeding, stroke, or kidney injury. Participants undergo procedures to treat non-culprit lesions (NCLs) using either physiology guidance or angiography guidance. In the physiology-guided group, percutaneous coronary intervention (PCI) is performed on lesions with resting full-cycle ratio (RFR) of 0.89 or less or fractional flow reserve (FFR) of 0.80 or less, according to local practice. The angiography-guided group receives PCI based on imaging assessments following local practice. The study includes an observational imaging sub-study using optical coherence tomography (OCT) for a subset of patients. Participants are involved for a minimum of two years, during which researchers monitor the time to first cardiovascular events such as death, new MI, or additional revascularization, along with safety events like bleeding or stroke. The study includes regular evaluations and follow-up to assess these outcomes, ensuring comprehensive safety and efficacy data collection in this patient population.

Researchers are investigating the safety and effectiveness of adding olaparib, a PARP enzyme inhibitor, to platinum-based chemotherapy given before surgery in patients with triple-negative breast cancer (TNBC) and/or those with germline BRCA (gBRCA) mutations. This randomized phase II/III trial aims to see if this combined treatment improves the rate of pathological complete response (pCR) at surgery while monitoring safety outcomes. The study plans to enroll at least 780 patients, including a minimum of 220 with gBRCA mutations. Participants will receive a minimum of 21 weeks of chemotherapy followed by surgery. The treatment includes oral olaparib tablets taken twice daily about 12 hours apart, alongside intravenous paclitaxel and carboplatin given in cycles every three weeks. During the trial, standard supportive care like granulocyte-colony stimulating factor and anthracyclines may also be administered. For those with residual disease after initial treatment, there is an option to join a sub-study involving additional chemotherapy drugs. Throughout the study, patients will undergo screenings including BRCA mutation testing and various tumor marker assessments. Safety will be closely monitored by the trial team and an independent committee. The main outcomes measured are treatment-related side effects, pCR rates after surgery, and long-term efficacy assessed over approximately 5.5 years, with follow-up planned for up to 10 years after surgery.