Kettering

Researchers are evaluating whether less frequent dosing of pembrolizumab after six months of standard treatment is safe and effective for patients with advanced non-small cell lung cancer NSCLC. Pembrolizumab, an immunotherapy targeting the PD-1 receptor, has improved outcomes in NSCLC, but current dosing every six weeks for up to two years may result in overtreatment. This UK phase III trial aims to find if reducing dose frequency can maintain effectiveness while improving quality of life and lowering costs. Participants who have received six months of pembrolizumab, with or without chemotherapy, and plan to continue treatment will be randomized to receive pembrolizumab intravenously every six weeks control or every twelve weeks initially. If the 12-week dosing is found to be not less effective, additional groups receiving doses every nine, fifteen, and eighteen weeks will be included. Patients who experience disease progression while on reduced frequency dosing can return to the standard six-week schedule. Throughout the study, participants will be monitored for overall survival at 18 months from randomization, along with other outcomes such as progression-free survival, response rate, duration of response, and adverse events over two years. The study involves regular hospital visits for treatment and assessments, and the results may lead to safer, more convenient treatment options for NSCLC patients. The total participation time varies depending on individual treatment and follow-up schedules.

Researchers are evaluating ziltivekimab, a new medicine not yet approved anywhere, to see if it can help people who were hospitalized due to a heart attack. The study aims to find out if ziltivekimab can reduce the development of heart disease and prevent future heart attacks or strokes. This is a Phase 3 clinical trial comparing ziltivekimab to a placebo in patients with acute myocardial infarction. Participants will receive an initial loading dose of ziltivekimab or matching placebo by injection under the skin as soon as possible after an invasive heart procedure, within 36 hours for STEMI or 48 hours for NSTEMI patients. After the loading dose, they will get monthly injections of the same study medicine for up to two years, in addition to their standard care. During the study, participants will be monitored for major cardiovascular events such as heart attack, stroke, and cardiovascular death. Researchers will also track other heart-related outcomes and safety measures over a period of up to 25 months. The study involves regular visits for injections, assessments, and laboratory tests to evaluate the medicines effects and patient health throughout the trial.

Researchers are studying colorectal cancer and colorectal adenomas to identify factors that best predict patients at high risk and to develop a risk prediction model. This observational study is national and multi-centre, focusing on patients undergoing colonoscopy either as part of the Bowel Cancer Screening Programme or due to symptoms. It addresses the limitation that current screening mainly considers age and aims to include other risk factors like smoking, alcohol use, family history, obesity, and gut bacteria composition. Participants will be divided into two groups one group of 10,000 patients referred for colonoscopy will provide detailed health and lifestyle information, including blood, stool, and saliva samples for various tests. Another group of 10,000 patients from the North of England will consent to be contacted for future research studies, providing some health information for this purpose. The study collects data on colonoscopy results, lifestyle factors, and patient experiences through questionnaires. During the study, patients will undergo measurements such as height, weight, and waist circumference, and complete health and food frequency questionnaires. Researchers will analyze colonoscopy findings, stool microbiome patterns, and biological samples to develop a risk prediction model for colorectal neoplasia. The study also aims to establish a platform of patients willing to participate in future research, with all results and patient consents tracked over a five-year period.

Sepsis is a serious condition caused by the bodys extreme response to an infection, leading to tissue and organ damage. This research compares two early treatment methods for sepsis immediately after hospital arrival, focusing on whether starting vasopressor medication right away or beginning with fluid therapy improves patient recovery and reduces complications. The study is a Phase 3 trial aimed at finding the best approach to improve outcomes for adults with septic shock. Participants are divided into two groups one receives a continuous peripheral vasopressor infusion of norepinephrine during the first 48 hours, while the other group receives standard care guided by UK NICE and Surviving Sepsis Campaign guidelines, which starts with intravenous fluids and adds vasopressors as needed. Both treatments follow local hospital protocols beyond the initial interventions. During the study, participants will be closely monitored for blood pressure, fluid volume, lactate levels, and other health indicators at multiple time points up to 90 days after randomization. Researchers will assess outcomes including hospital stay length, need for additional therapies like renal replacement or respiratory support, and overall survival. Quality of life and readmission rates will also be evaluated to understand the longer-term effects of the treatments.

Researchers are evaluating the safety and effectiveness of the Shockwave Reducer device in patients with refractory angina pectoris who have persistent symptoms despite receiving the best medical therapy. This study includes a randomized, double-blinded, sham-controlled trial as well as a non-randomized registry for specific patient groups, such as those with right coronary artery ischemia or those unable to complete exercise tests. The trial aims to compare outcomes between patients receiving the device implant and those undergoing a sham procedure, focusing on those unsuitable for standard revascularization procedures. Participants in the randomized trial will be assigned to either receive the Shockwave Reducer implant or a sham implantation procedure without the device. Patients in the single-arm registry will receive the Shockwave Reducer device without randomization. The study involves detailed assessments including coronary angiography and functional tests to confirm eligibility. The treatment period and follow-up extend through six months to evaluate both safety and effectiveness outcomes. During the study, participants will undergo multiple evaluations including stress tests, imaging, and clinical assessments to monitor angina symptoms and cardiac function. Researchers will track key outcomes such as angina severity scores and safety endpoints at six months. Participants are expected to comply with follow-up visits and stable medication regimens, and the study includes careful monitoring to ensure adherence and collect comprehensive data on the devices impact on refractory angina symptoms.

Researchers are evaluating treatments for high-risk polycythemia vera PV, a blood condition. This phase III international trial compares the drug ruxolitinib against the best available therapy, which includes hydroxycarbamide or any form of interferon alpha, chosen by the doctor before randomization. The study aims to determine which treatment better prevents serious complications and improves patient outcomes over about three years. Participants will be randomly assigned to one of two groups one receiving oral ruxolitinib 10 mg twice daily, and the other receiving either hydroxycarbamide or interferon alpha via standard hospital care. There is no switching between treatments during the study. The trial is open-label, meaning both doctors and participants know which treatment is given. During the trial, participants will have regular assessments including blood tests, symptom and quality of life questionnaires, and monitoring for events like thrombosis, bleeding, or disease progression. Researchers will track treatment side effects, blood markers, spleen size, and time between blood removal procedures. The study duration is approximately three years per participant, with some outcomes followed up to eight years to assess long-term effects and health economics.

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 evaluating treatments for community-acquired pneumonia CAP, especially in patients admitted to intensive care units ICUs. This trial also adapts to study treatments for respiratory pandemics like COVID-19. The goal is to determine which treatment strategies improve outcomes for patients with severe pneumonia, using a flexible, ongoing approach that can test multiple therapies simultaneously and update as new information becomes available. Participants receive different treatment strategies based on random assignment to study groups. Treatments include various antibiotics, steroids, antivirals, immune modulators, anticoagulation methods, and ventilation strategies. Some treatment options have been closed to recruitment, reflecting the trials adaptive nature. The trial includes several domains targeting specific infections such as influenza and COVID-19, with dosing and duration guided by clinical practice and local guidelines. During the study, participants are monitored closely with assessments including survival up to 90 days, days alive without organ support in ICU, ICU and hospital length of stay, ventilator-free days, organ failure-free days, and quality of life up to 6 months. Researchers collect detailed data on patient outcomes, organ support needs, and hospital discharge status. The study runs until February 2028, with ongoing evaluation to improve pneumonia treatment strategies in ICU settings and during respiratory pandemics.

Bicuspid aortic valve BAV is the most common congenital heart valve anomaly affecting 1-2% of the population. This condition causes the aortic valve to have two leaflets instead of three, which can restrict blood flow or cause leakage, leading to strain on the heart. BAV is linked to serious health issues and early mortality, often requiring surgical valve replacement. It tends to run in families and likely has a genetic cause, but the specific genes involved are not well understood. This study aims to identify genetic variants associated with BAV using advanced DNA sequencing techniques. It recruits patients diagnosed with BAV as well as their first-degree relatives, who may or may not have the condition. An additional group of unrelated healthy individuals with normal three-leaflet valves will be included for comparison. Participants will undergo echocardiographic screening to detect BAV and provide blood samples for genetic analysis. Participants will complete questionnaires and allow access to their medical records to collect demographic and clinical data. Blood samples will be analyzed to identify genetic variants linked to BAV by comparing those with and without the condition within families and between patient and control groups. The primary outcome is to find genetic loci associated with BAV over a 48-month period, which could improve understanding and management of this heart condition.

Aortic stenosis AS affects many older adults, with a rising number of people over 65 and 75 years old experiencing moderate to severe disease. This study aims to compare the benefits of early aortic valve replacement AVR versus expectant management in patients with severe asymptomatic AS. It addresses a significant gap, as no randomized controlled trials have yet compared these approaches to determine which leads to better outcomes and cost-effectiveness. Participants will be randomly assigned to either early AVR, where surgery or transcatheter AVR TAVI is planned within six months, or to expectant management, involving regular monitoring according to standard hospital practice. The study will be conducted across multiple centers in the UK, Australia, and New Zealand, with an internal pilot phase to confirm recruitment feasibility. Those in the AVR group may undergo additional tests such as coronary angiography, with further treatment decisions made by their care team. During the study, participants will be followed for a median of 5.5 years, with assessments including cardiovascular events, hospitalizations, quality of life questionnaires, and health economics evaluations. Researchers will measure a combined outcome of cardiovascular death, heart failure hospitalization, and stroke, along with other health and disability measures. The study will use intention-to-treat analysis, ensuring participants are evaluated in their assigned groups regardless of treatment received.