Paisley

Researchers are evaluating the use of Targeted Sentinel Node Biopsy (TSNB) in patients with breast cancer who have limited nodal disease. This study focuses on patients with biopsy-confirmed axillary nodal metastases and aims to audit surgical outcomes of TSNB against sentinel node biopsy outcomes, arm lymphoedema rates, and disease progression. The research highlights the importance of assessing nodal tumour burden and compares TSNB with other treatments like axillary lymph node dissection (ALND) and axillary radiotherapy (ART). Previous trials like AMAROS, OTOASOR, and POSNOC provide background on nodal treatment strategies and outcomes. Participants will undergo TSNB during primary surgery, where at least three lymph nodes, including a marked biopsy-proven positive node, are removed. Node marking can be done at biopsy or a separate visit using various techniques such as clips, dyes, or magnetic markers. The procedure follows a standardized approach adapted from the ATNEC trial, with either dual- or single-tracer sentinel node biopsy methods. If the marked node is not found or multiple black nodes appear, removal may stop after four nodes. The study focuses on patients with one or two macrometastases identified in the removed nodes. During the study, patients will be monitored for outcomes including the number of nodal macrometastases over 12 to 60 months, the identification rate of the marked node, and the false negative rate of the TSNB procedure. Arm lymphoedema will also be assessed up to 60 months. This audit collects data to benchmark surgical outcomes and evaluate arm morbidity and disease progression compared to existing trials, aiming to establish TSNB as a reliable staging method in this patient group.

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 studying new diagnostic biomarkers on the LumiraDx Platform to improve the ability of clinicians and patients to monitor chronic health conditions such as embolism, infection or inflammation, cardiovascular, and renal diseases. This research compares these new biomarkers to gold standard reference methods, aiming to deliver faster results at the point of care. The study involves up to 20,000 patients from various medical settings, including emergency departments, hospital wards, and outpatient clinics. Participants will have blood samples collected in two phases depending on research needs. In Phase 1, only venous blood samples will be drawn and tested on the LumiraDx system and compared to reference methods. In Phase 2, both venous blood and capillary fingerstick samples will be collected and tested similarly. Sample processing may occur at clinical sites or LumiraDx UK Ltd. Samples will be anonymized and stored for future testing and development of biomarkers such as Troponin, NT-pro BNP, BNP, D-Dimer, and others. Each participant's involvement lasts up to 45 minutes per visit, with a maximum of 24mL of venous blood and 6 fingersticks collected within three months. Patients may be asked to participate again at subsequent visits, with a total sample limit maintained. Data collected includes demographics, medical history, medications, test results, and diagnoses. Blood samples will be measured using both the new LumiraDx method and standard reference methods over a period of up to five years to assess biomarker performance and device calibration.

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 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.

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.

The trial investigates the role of ixazomib in patients with relapsed multiple myeloma who have previously undergone autologous stem cell transplant (ASCT). This phase III, open-label, randomized, controlled study aims to evaluate whether adding a proteasome inhibitor to the salvage ASCT conditioning improves the depth of response, and to assess the impact of consolidation and maintenance treatments on the durability of response. The study also looks at overall survival, progression time, quality of life, and treatment safety among participants with measurable disease and good performance status. All participants first receive re-induction therapy consisting of 4 to 6 cycles of ixazomib, thalidomide, and dexamethasone (ITD) over 28-day cycles to achieve maximum disease control. Those who reach stable disease or better are randomized to receive either conventional ASCT using melphalan or augmented ASCT combining melphalan with ixazomib. Following this, participants who maintain minimal response or better undergo a second randomization to either receive consolidation therapy with 2 cycles of ITD followed by ixazomib maintenance until disease progression, or no further treatment. During the study, participants will undergo regular assessments including blood tests, disease response evaluations, and monitoring for adverse effects. The primary outcomes measured are overall response rate 100 days after ASCT and progression-free survival up to 10 years. Secondary evaluations include overall survival, time to disease progression, minimal residual disease status at various stages, engraftment kinetics, and quality of life. Follow-up continues with clinic visits every three months until disease progression is observed, enabling long-term monitoring of treatment effects and safety.