Kettering

Researchers are evaluating whether reducing the frequency of pembrolizumab treatment after six months of standard therapy is safe and effective for patients with advanced non-small cell lung cancer (NSCLC). Pembrolizumab, an immunotherapy targeting the PD-1 receptor on T cells, has improved outcomes for this condition. Because pembrolizumab remains bound to its target for a long time and dosing frequency may not affect outcomes, this study aims to find out if less frequent dosing can maintain effectiveness while reducing overtreatment and side effects. This phase III study also considers potential benefits like cost savings and improved quality of life due to fewer hospital visits. Participants who have completed six months of pembrolizumab treatment without disease progression and are continuing therapy will be randomly assigned to receive pembrolizumab at the standard six-week interval or at a reduced frequency of 12 weeks. If early results show that the 12-week schedule is not less effective, later participants may be randomized to even longer intervals of 9, 15, or 18 weeks. Pembrolizumab is given intravenously at 400 mg per dose. Patients whose disease progresses on a reduced frequency schedule may return to the standard six-week treatment. During the study, researchers will monitor overall survival at two years after randomization. Participants will undergo regular assessments to track disease status, treatment tolerability, and overall health. The study aims to confirm that less frequent dosing does not reduce survival while potentially improving patient experience. The trial is open to adults aged 18 and older with advanced NSCLC who have already completed six months of pembrolizumab therapy and intend to continue treatment.

Researchers are evaluating whether ziltivekimab can help people who were hospitalized due to a heart attack by potentially reducing the development of heart disease and preventing new heart attacks or strokes. This Phase 3 study compares ziltivekimab with a placebo, which is a dummy medicine that has no effect on the body. Both treatments are given by chance, with equal likelihood for participants to receive either ziltivekimab or placebo. Participants will inject the study medicine once a month under the skin in the stomach, thigh, or upper arm. Ziltivekimab is given as an initial loading dose followed by monthly maintenance doses. The placebo group receives a matching injection schedule. The study duration is about two years. During the study, researchers will monitor participants for the time until the first serious heart-related event, including cardiovascular death, non-fatal heart attack, or non-fatal stroke. Participants will be closely observed from the start of randomization up to 25 months. The study includes regular follow-ups to assess safety and effectiveness of the treatments throughout this period.

Researchers are conducting a national multi-center study over five years to identify factors that best predict patients at high risk for colorectal cancer or colorectal adenomas. This study aims to develop a risk prediction model that considers various risk factors beyond age, such as smoking, alcohol use, family history, obesity, and gut bacteria composition. The study will recruit 10,000 patients undergoing colonoscopy either through the Bowel Cancer Screening Programme or due to symptoms, with a further 10,000 patients from the North of England consenting to future research contact. Participants will undergo diagnostic colonoscopy and complete health questionnaires. Measurements such as height, weight, and waist circumference will be taken. Blood, stool, or saliva tests will also be collected depending on the colonoscopy indication. Results from colonoscopies and any samples taken will be compiled. Additionally, patients will complete a patient experience questionnaire or food frequency questionnaire. The study will explore the role of gut bacteria in patients with adenomas or cancer to enhance the risk prediction model. Participants will be monitored for the occurrence of colorectal neoplasia over five years. The study will collect and analyze data from questionnaires, laboratory tests, and colonoscopy findings to evaluate risk factors. Safety and patient experience will be assessed through questionnaires. The study also plans to build a large patient platform for future research opportunities, aiming to improve early detection and personalized risk assessment for colorectal cancer.

Researchers are evaluating two different early treatment methods for adults hospitalized with sepsis, a serious condition caused by the body's extreme response to infection. This study focuses on comparing starting a vasopressor medication called norepinephrine immediately versus the standard approach of first giving fluid through a drip and then adding vasopressors if needed. The goal is to see which method better improves recovery, reduces complications, shortens hospital stay, and enhances long-term health. This is a Phase 3 clinical trial addressing a critical and complex condition with significant risks to patients' organs and survival. The study compares early peripheral vasopressor infusion (PVI) started within 12 hours of hospital admission targeting a mean arterial pressure (MAP) of 65 mmHg or higher, against the usual care involving intravenous fluids followed by vasopressors as needed. Norepinephrine is prepared at a concentration of 16 micrograms/ml and administered either as an early continuous infusion or after fluid resuscitation. Balanced crystalloid fluids are given according to standard care practices. Current guidelines and clinical practices inform the treatment approach, but this study aims to clarify the benefits of early vasopressor use in septic shock. Participants will be monitored for clinical effectiveness during the first 48 hours, with follow-up extending to 90 days after randomization. The study includes assessments such as blood pressure, serum lactate levels, and clinical status evaluations. Researchers will track recovery times, complications, hospital length of stay, and long-term health outcomes. Safety monitoring and evaluation of adverse effects will be ongoing throughout the study period to ensure participant well-being.

Researchers are evaluating the safety and effectiveness of the Shockwave Reducer, an implantable device, for treating patients with refractory angina pectoris who continue to have symptoms despite receiving the best possible medical therapy. The study includes patients with evidence of reversible myocardial ischemia in the left coronary artery distribution who are not suitable for revascularization. Additionally, a non-randomized single-arm registry will assess the device in patients with ischemia in the right coronary artery, those without obstructive coronary disease but abnormal coronary flow reserve, and those unable to complete exercise testing due to limb amputation or mobility issues requiring walking aids. The study is a multicenter, randomized, double-blinded, sham-controlled trial with three groups. One group receives the Shockwave Reducer implant, another undergoes a sham implantation procedure without device placement, and a third group participates in a non-randomized registry receiving the device. The device is implanted in the coronary sinus, and patients continue their stable anti-anginal medication regimen. The study monitors outcomes over six months after implantation. Participants will be evaluated through various tests including stress echocardiography, nuclear imaging, PET, MRI, CT perfusion, and physiological assessments to confirm reversible ischemia. They will also undergo exercise tolerance tests, echocardiography to assess heart function, and angiography. Researchers will measure effectiveness and safety endpoints at six months. Follow-up visits and tests will ensure adherence and monitor for any adverse events. Total participation includes screening, treatment, and follow-up over at least six months.

Researchers are conducting a phase III, randomized, open-label, international trial to compare ruxolitinib with the best available therapy for patients with high-risk polycythemia vera (PV). The best available therapy includes either interferon alpha or hydroxycarbamide, selected by the investigator before randomization. This study aims to evaluate which treatment better prevents major complications like thrombosis, hemorrhage, or progression to more severe blood disorders within approximately three years. Participants will be randomly assigned to receive either ruxolitinib at a dose of 10 mg twice daily or best available therapy consisting of interferon alpha or hydroxycarbamide, administered through standard hospital methods. There will be no crossover between treatment arms during the trial. Interferon formulations, including pegylated-interferon, may be used at the investigator's discretion. During the study, participants will be monitored for event-free survival, defined as the time until the first major thrombosis, hemorrhage, death, or disease transformation. Assessments will include regular clinical evaluations and laboratory tests over the approximately three-year trial period. The trial emphasizes safety and effectiveness by closely observing patient outcomes and treatment tolerability throughout the study.

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 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.

Bicuspid aortic valve (BAV) is the most common congenital heart valve condition, affecting 1-2% of people. Instead of the usual three leaflets, the aortic valve has two, which can cause it to either not open fully or leak, putting strain on the heart. This condition increases the risk of serious complications and often requires surgery. BAV tends to run in families and is believed to have a genetic cause, but the exact genes and inheritance patterns are not fully known. The BRAVE study aims to discover the genetic changes linked to BAV to better understand its development and impact. The study recruits patients diagnosed with BAV and their first-degree relatives, whether or not they have BAV. Participants undergo echocardiography screening, and blood samples are collected for detailed genetic analysis using advanced DNA sequencing techniques. The study also includes a control group of healthy individuals with normal three-leaflet valves to compare genetic differences. Researchers will analyze genetic variants to find those more common in people with BAV or within affected families, combining case-control and family-based approaches. Participants provide demographic and clinical information via questionnaires and medical records, including imaging results. Blood samples may also be used for additional laboratory tests to support genetic findings. The primary goal is to identify genetic locations associated with BAV over a 48-month period. This comprehensive approach helps researchers understand the genetic basis of BAV, potentially improving future management of this heart valve condition.