Shrewsbury

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 combined Phase 2b and Phase 3 clinical trial to study CSL300 Clazakizumab in adults with end stage kidney disease ESKD who are undergoing maintenance dialysis. The study aims to find the right dose of CSL300 and then evaluate its effect on cardiovascular outcomes and safety in people with systemic inflammation and either atherosclerotic cardiovascular disease ASCVD or diabetes. This is a randomized, double-blind, placebo-controlled study involving multiple centers. Participants will receive intravenous IV administration of either CSL300 or a placebo. The Phase 2b part focuses on determining the appropriate dose of CSL300 compared to placebo over about 12 weeks, while the Phase 3 part examines CSL300s effect on cardiovascular events over approximately five years. The study includes different dosing groups in Phase 2b and a larger comparison of CSL300 versus placebo in Phase 3. During the study, participants will be monitored regularly with blood tests that measure inflammation markers such as high-sensitivity C-reactive protein hs-CRP, cardiovascular events, and safety outcomes. Researchers will track changes in various blood components and adverse events up to 32 weeks in Phase 2b and follow cardiovascular outcomes for up to five years in Phase 3. The total participation lasts through these periods with scheduled assessments to evaluate treatment effects and safety.

Researchers are evaluating the effects of a medicine called BI 690517 combined with empagliflozin in adults with chronic kidney disease CKD who are at risk of their kidney condition getting worse. The study includes people with or without type 2 diabetes and those who may already be taking medicines like angiotensin converting enzyme inhibitors ACEi, angiotensin receptor blockers ARB, or sodium-glucose cotransporter-2 inhibitors SGLT2i. The goal is to understand if adding BI 690517 can help delay worsening kidney function, hospitalizations due to heart failure, or cardiovascular death. After a run-in period where all participants take empagliflozin and other standard medications, participants are randomly assigned to receive either BI 690517 tablets or placebo tablets once daily alongside empagliflozin. The run-in period confirms that participants are stabilized on empagliflozin before randomization. The treatment phase continues for about three to four years until enough kidney or heart-related events have occurred to compare outcomes between the two groups. During the study, participants visit the study site about five times in the first six months and then every six months thereafter. At these visits, health is regularly checked through blood and urine tests, blood pressure and weight measurements, kidney function monitoring, and collection of any side effect information. The main outcome measured is the time until the first occurrence of kidney disease progression, hospitalization for heart failure, or cardiovascular death.

This research aims to evaluate the effects of lowering blood phosphate levels in adults with end-stage kidney disease ESKD who are receiving dialysis. Elevated phosphate levels are common in ESKD and linked to higher risk of death and heart problems, but it is unclear if reducing phosphate improves important patient outcomes. The study will compare intensive lowering of phosphate to a more liberal phosphate target to see if this reduces heart-related deaths and events, improves physical health, and is cost-effective. Participants will be randomly assigned to one of two groups one aiming for a liberal serum phosphate target of 2.0 to 2.5 mmolL, and the other aiming for an intensive target of 1.50 mmolL or lower. Doctors will decide the type and dose of phosphate-lowering medications to help participants reach their assigned phosphate levels, following usual local practices. The study will last up to five years and is conducted internationally with 3600 adults on dialysis. During the study, researchers will monitor participants for major heart-related events and deaths, physical health, fatigue, quality of life, patient satisfaction, and itching. Regular assessments will include measuring time to cardiovascular death or major cardiovascular events and evaluating overall survival and quality of life using the EQ5D-5L tool. The study will also assess cost-effectiveness and continue to observe participants for five years to collect comprehensive data on these outcomes.

Researchers are evaluating the impact of two different default dialysate sodium concentrations on major cardiovascular events and death in adults receiving maintenance haemodialysis for end-stage kidney disease. This pragmatic, cluster-randomised, open-label Phase 4 study compares sodium levels of 137 mmoll and 140 mmoll in real-world dialysis settings across multiple sites globally. Dialysis sites will be randomly assigned to use either a default dialysate sodium concentration of 137 mmoll or 140 mmoll for at least 90% of dialysis sessions. Other aspects of patient care will follow standard local practices. Sites must consent to participate, and individual patients will provide waiver or opt-out consent. The study expects to enroll sites over 5 to 7 years, with each participant followed for approximately 2 to 5 years until the study endpoints are reached. Participants will receive dialysis at their assigned sites with the designated sodium concentration. Researchers will monitor the time to first occurrence of major cardiovascular events or death as the primary outcome. Secondary outcomes include other cardiovascular events and individual components of the composite outcomes. Data collection and patient monitoring will continue throughout the study period, estimated to last around five years per participant.

Researchers are studying patients with newly diagnosed stage I, II, and III colorectal cancer CRC to understand how circulating tumor DNA ctDNA in the blood can predict disease relapse. The study evaluates whether using ctDNA to guide adjuvant chemotherapy decisions after surgery is as effective as standard chemotherapy, aiming to reduce unnecessary treatments and side effects. This multi-center, prospective research includes both observational and randomized components to better manage early-stage CRC. The study has two parts Part B focuses on collecting tumor tissue, serial blood samples, and clinical data to detect minimal residual disease MRD using ctDNA after curative surgery. Part C is a randomized trial comparing ctDNA-guided adjuvant chemotherapy versus standard care in patients with high-risk stage II or III CRC. Patients are randomized post-surgery to either standard chemotherapy or a ctDNA-guided approach where those testing negative for ctDNA may receive less chemotherapy. Participants will undergo regular blood sampling and clinical assessments to monitor ctDNA levels and disease status. Researchers will measure outcomes such as 3-year disease-free survival and the relationship between ctDNA detection and treatment response over several years. The study includes follow-up periods of 4 to 8 years to evaluate long-term outcomes and safety. Participants need to consent, adhere to follow-up schedules, and be suitable for chemotherapy if randomized to Part C.

Idiopathic pulmonary fibrosis IPF is a progressive lung disease causing scarring that leads to coughing and breathlessness. Many IPF patients also have reflux disease, where stomach acid can damage the lungs. This research aims to find out if treating IPF patients with proton pump inhibitors PPIs, which reduce stomach acid, can slow down the progression of IPF. The trial is a randomized, placebo-controlled study involving 298 IPF patients across about 37 UK hospitals. Participants will be randomly assigned to take either lansoprazole a PPI or dummy tablets twice daily for 12 months. They will start weekly breathing tests at home using equipment provided and, if they have a cough, use a device to count coughs over 24 hours. Participants will complete questionnaires about coughing, breathlessness, sleep habits, and overall health. Some will also wear activity and sleep monitors during cough monitoring sessions. Dose reduction is allowed if side effects occur. During the study, patients will complete regular questionnaires and provide blood samples for safety checks at 3, 6, 9, and 12 months. Weekly home spirometry will continue for the full year. Researchers will track lung function, cough frequency and severity, breathlessness, quality of life, sleep quality, reflux symptoms, and hospital-free survival. Remote and in-person visits are possible, and participants will receive training on study procedures. The primary outcome is the change in lung function 12 months after starting treatment.

The trial investigates whether stopping or continuing milk feeding around the time of blood transfusion in very premature infants born before 30 weeks gestation affects the risk of developing Necrotizing Enterocolitis NEC, a serious intestinal disease. NEC can cause severe damage or death in preterm infants, and this study aims to find out which feeding approach during transfusion may reduce this risk. The trial is conducted in neonatal intensive care units across Canada and the UK and compares two standard care methods currently in use. Participants are randomly assigned to one of two groups one group will stop all enteral feeds for 4 hours before, during, and 4 hours after packed red cell transfusions, with hydration maintained by intravenous nutrition or glucose the other group will continue feeding as usual throughout the transfusion period. Infants stay in their assigned feeding group until they reach 34 weeks and 6 days gestational age. This approach follows practices identified as acceptable in prior surveys and studies. During the study, infants will be closely monitored for the development of NEC and other health outcomes from randomization until 40 weeks postmenstrual age. Researchers will track serious complications like severe NEC, infections, growth, lung disease, eye problems, brain injury, and hospital stay duration. The study collects detailed information about feeding, infections, nutrition, and clinical status to evaluate the safety and effects of each feeding strategy during transfusion.