Gateshead

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 investigating whether encapsulated faecal microbiota transplantation (FMT) can help reduce infections and mortality in adults with alcohol-related or metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis. Cirrhosis, a severe scarring of the liver, is a growing health crisis, leading to high rates of early death, with infections being a major complication. Previous trials showed that FMT delivered endoscopically is safe, and this study aims to test a capsule form of FMT to improve patient outcomes without the need for invasive procedures. Participants will be randomly assigned to receive either encapsulated FMT or placebo capsules that look identical. They will take five capsules every three months for up to 21 months or until they develop an infection requiring hospital admission. This double-blind trial will follow participants for up to 24 months to compare infection rates and time to hospitalization between the two groups. The study will also explore if FMT improves liver function, immune response, and reduces harmful bacteria linked to cirrhosis complications. During the study, participants will be closely monitored for infections and other cirrhosis-related complications through hospital visits and assessments. Researchers will measure the time until the first infection or decompensation leading to emergency or hospital admission. Laboratory tests will evaluate immune system changes and the presence of antibiotic-resistant bacteria. The trial will last up to two years, aiming to provide insights into new, antibiotic-free treatments for cirrhosis and influence future care and policy.

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.

This research aims to understand the genetic factors that contribute to the risk of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). GCA is a serious inflammatory disease affecting blood vessels, mainly in people over 50, which can cause severe complications like vision loss or stroke if untreated. PMR causes pain and stiffness in the limbs with signs of inflammation. The study involves both patients recently suspected of having GCA and those with confirmed diagnoses from the past. It seeks to provide new insights into disease causes and improve diagnosis and treatment approaches. Participants are observed in a multi-center study collecting clinical and genetic data. The study includes both prospective patients with suspected GCA and retrospective patients with confirmed GCA or PMR diagnoses. Some retrospective participants receiving tocilizumab for recurring or difficult-to-treat GCA are also included in a safety monitoring registry. Data collected include clinical features, imaging, tissue and blood samples, and advanced genetic testing. The study also follows patients over time to assess disease impact, quality of life, and long-term outcomes. During the study, participants provide medical information, biological samples, and complete questionnaires about their symptoms and quality of life. Researchers monitor disease activity and treatment effects, especially among those starting certain immune-modifying drugs. The main measurements focus on genetic susceptibility at the study start, with ongoing evaluation of diagnosis, prognosis, and disease progression. The study is designed to improve understanding and management of GCA and PMR over time.

Acute respiratory infections (ARI) are common reasons for hospital admission and use of antibiotics, caused by various pathogens including viruses like influenza and coronaviruses. This research aims to describe how adults with ARI are diagnosed and treated in emergency rooms and acute hospital settings across Europe, focusing on understanding the different routine practices and clinical outcomes. The study also seeks to identify the causes of ARI in these patients to aid in improving care and targeting treatments better. The study involves collecting data on diagnostic methods and treatments used for ARI from adults presenting to emergency departments or acute medical units. This includes patients admitted to the hospital as well as those discharged the same day. Some participants will provide a research sample from the upper respiratory tract within 24 hours of enrollment to detect pathogens using molecular tests. Data collection will detail clinical information, laboratory results, and medication use to understand variations across hospitals. Participants will be monitored for up to four years, with measures including the proportion undergoing relevant microbiology and virology tests, use of antibiotics and other medications, hospital and ICU length of stay, duration of respiratory support, and mortality. Clinical outcomes will be recorded up to 28 days after admission or until discharge or death. This long-term observational study aims to support better diagnosis and treatment strategies to reduce antimicrobial resistance and improve patient outcomes.

Researchers are evaluating a range of treatments to improve outcomes for adults admitted to intensive care units (ICUs) with severe community-acquired pneumonia (CAP), including cases caused by influenza and COVID-19. This Phase 3 adaptive platform trial, REMAP-CAP, is designed to test multiple treatment strategies simultaneously and adapt over time, allowing new treatments to be added as questions are answered. The trial also serves as a platform to quickly evaluate treatments during respiratory pandemics, such as COVID-19, through a sub-study called REMAP-COVID in the United States. Participants receive various interventions including antibiotics like ceftriaxone, moxifloxacin, or piperacillin-tazobactam, as well as macrolide therapies given for different durations. Other treatments assessed include corticosteroids such as hydrocortisone and dexamethasone, antiviral agents like oseltamivir and remdesivir, immune modulators including tocilizumab and baricitinib, and supportive care strategies such as mechanical ventilation methods. Dosing and duration vary for each treatment, with some interventions now closed. Treatments are administered according to local guidelines and clinical decisions, with some requiring intravenous or enteral routes. Participants are closely monitored with assessments focusing on survival and organ support status in the ICU up to 90 days after enrollment. The main outcomes measured include all-cause mortality by day 90 and the number of days alive without needing organ support in the ICU by day 21. The study collects data continuously to adapt treatment assignments for new participants, aiming to identify the most effective therapies. Follow-up and safety monitoring continue throughout hospitalization and up to 90 days after admission.

Researchers are exploring new methods to improve the early diagnosis of lung cancer by analyzing blood samples from participants. This study aims to create tools that make it easier to screen individuals with possible lung health issues, diagnose problems earlier with fewer tests, and begin effective treatments sooner. The study is linked with the DART study and uses artificial intelligence to support faster and more accurate diagnosis of lung problems, including lung cancer. Blood samples collected from participants will be used to develop computer programs called algorithms that analyze medical data. These algorithms are trained to detect lung health problems and can assist doctors in identifying issues more quickly and accurately. The goal is to improve lung health care by integrating AI with existing screening programs. Participants will have their blood samples collected and linked with data from CT scans and other lung health checks. The study will monitor how well these AI-based tools perform in diagnosing lung cancer compared to current methods. The primary outcome is to develop an algorithm that improves lung cancer diagnosis by February 2025. Participant involvement includes providing consent and undergoing lung cancer screening procedures as part of the Lung Health Check programme.

Chronic obstructive pulmonary disease (COPD) is a common lung condition affecting about 10% of adults worldwide, with a prevalence of 4.5% in those aged 40 years and older in the UK. Exacerbations, or sudden worsening episodes often triggered by infections, can lead to hospital admissions and carry risks of increased illness and death. This trial focuses on the high-risk 90-day period after hospital discharge, during which patients have a 43% chance of readmission and 12% risk of mortality. The study aims to test whether a supported rescue pack management plan can reduce readmissions by 20%. This is a Phase 3, open-label, multicenter randomized controlled trial involving 1400 patients across 30 NHS trusts.

Aortic stenosis (AS) affects a significant portion of the elderly population, with approximately 5% of those over 65 years old and around 3% of those over 75 years having moderate to severe AS. The number of people with AS is increasing rapidly due to an aging population, creating challenges for clinicians in managing mostly elderly patients who are often symptom-free but have severe AS diagnosed incidentally. While symptomatic severe AS requires aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI), the best approach for asymptomatic patients remains unclear. This trial aims to compare early AVR or TAVI with standard expectant management in these patients to provide evidence on clinical outcomes and cost-effectiveness. The study is a large, multi-center randomized controlled trial conducted in the UK, Australia, and New Zealand, with plans to expand internationally. It includes two phases: a vanguard phase and a main phase, with an internal pilot to ensure adequate recruitment over two years. Eligible participants with severe asymptomatic AS will be randomly assigned to either early AVR or ongoing surveillance (expectant management). Those in the early AVR group will undergo surgery within about three months, which may include additional procedures like coronary angiography and possible coronary interventions if needed. The trial uses intention-to-treat analysis to compare outcomes between groups. Participants will be closely monitored throughout the study, with evaluations including routine tests and assessments as part of their care. The primary outcome measured is a combination of cardiovascular death and hospitalization for heart failure over a minimum of three years. The study also collaborates with another trial, EVoLVeD, offering participants additional research opportunities. Overall, the study seeks to provide important data on whether early valve replacement before symptoms develop can improve outcomes for people with severe asymptomatic AS.

Researchers are evaluating the clinical characteristics, natural progression, disease outcomes, and underlying mechanisms of Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) through the European NAFLD Registry. This large, international observational study brings together clinical academics from leading European universities, aiming to understand why patients vary in disease severity and to develop and validate biomarkers that detect and monitor disease progression from NAFL to NASH, fibrosis, and cirrhosis. This non-interventional study collects detailed cross-sectional and longitudinal clinical data including laboratory tests, liver histology, comorbidities, medications, and imaging results. It also gathers biological samples such as blood, liver tissue, urine, and stool from adults with risk factors for NAFLD. Participants are recruited mainly through hepatology, diabetology, and bariatric surgery clinics across Europe. Data collected supports research into disease mechanisms through genetic and molecular analyses and biomarker development. With additional consent, participants may join nested sub-studies acquiring advanced imaging data. During participation, patients provide clinical information and biological samples, which are recorded anonymously. Researchers assess the detailed clinical phenotype of NAFLD patients in a one-day characterization. The registry facilitates collaborative research and aims to improve understanding and management of NAFLD and related conditions over time.