Paisley

Researchers are evaluating the use of Targeted Sentinel Node Biopsy TSNB in patients with breast cancer who have limited nodal disease and are undergoing primary surgery. The study focuses on patients with T1 or T2 tumors and biopsy-confirmed nodal metastases with up to two abnormal nodes on axillary ultrasound. The goal is to audit surgical outcomes of TSNB and compare them with outcomes from sentinel node biopsy and targeted axillary dissection after chemotherapy, assessing arm lymphoedema and disease progression over time. The intervention involves performing TSNB using either a dual- or single-tracer technique in line with protocols from the ongoing ATNEC trial. The marked biopsy-positive node and at least three nodes are removed during surgery. Node marking techniques may include clips, black dye, magnetic seeds, or reflectors, with the timing of marking either at biopsy or a separate visit. Axillary treatment after TSNB is determined by local multidisciplinary teams based on findings. Participants will be monitored for up to 60 months, with regular assessments including histology to identify nodal macrometastases, identification rates of the marked node, false negative rates of TSNB, and arm lymphoedema. Secondary outcomes include rates of axillary, regional, and local recurrence, disease-free survival, and overall survival. This long-term follow-up will help benchmark TSNB outcomes against previous trials and provide data on surgical morbidity and disease control.

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 conducting a study to develop and improve new diagnostic biomarkers using the LumiraDx Platform. This platform aims to enhance the ability of clinicians and patients to monitor chronic health conditions at the point of care by providing results comparable to approved gold standard methods. The study includes patients with conditions related to embolism, infection or inflammation, cardiovascular, and renal diseases. The study involves collecting blood samples from up to 20,000 patients, including venous blood and capillary fingerstick samples. Sample collection is divided into two phases Phase 1 collects venous blood tested using LumiraDx and reference methods, while Phase 2 includes both venous and fingerstick samples tested similarly. Samples will be anonymized and sent to LumiraDx UK Ltd for storage and future testing to optimize and calibrate new biomarkers. Participants will spend up to 45 minutes in the study, during which blood samples are collected, ideally alongside standard care blood draws. Data on patient demographics, medical history, and current medications will be recorded. The primary outcome is to measure blood samples from patients with various conditions using both reference and LumiraDx methods over up to five years. Patients may be re-sampled up to three months after initial consent, with limits on total blood volume collected.

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 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.

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.

The trial investigates the role of ixazomib in patients with relapsed multiple myeloma who have previously undergone autologous stem cell transplant ASCT. It is a phase III, randomized, controlled, multi-center, open-label study aiming to assess whether adding a proteasome inhibitor to salvage ASCT conditioning improves depth of response and how consolidation and maintenance therapy influence the durability of response. The study also evaluates overall survival, progression-free survival, response rates, minimal residual disease, toxicity, and quality of life. Participants first receive re-induction therapy with 4 to 6 cycles of ixazomib, thalidomide, and dexamethasone ITD, each cycle lasting 28 days. Those achieving at least stable disease are randomly assigned to receive either conventional ASCT using melphalan alone or augmented ASCT combining melphalan with ixazomib. After ASCT, participants with minimal response or better are further randomized to either receive consolidation with 2 cycles of ITD followed by ixazomib maintenance until disease progression or no further treatment. During the study, participants undergo regular assessments including response evaluation 100 days post-ASCT, monitoring of progression-free survival for up to 120 months, and measurement of minimal residual disease at several time points. Safety and toxicity are closely monitored throughout re-induction, post-ASCT, consolidation, and maintenance phases. Quality of life questionnaires are completed at baseline, post-re-induction, post-ASCT, and during follow-up visits up to 24 months. The study plans to register 406 participants, with 284 randomized at the first stage and 248 at the second stage.