Grimsby

Researchers are evaluating the optimal duration of antibiotic treatment for adults with complicated intra-abdominal infections (cIAI). This Phase 3 trial aims to compare a fixed extended duration of 28 days of antibiotics to the current standard care durations, which typically range from 7 to 18 days. The study will assess clinical outcomes, quality of life, and cost effectiveness over a 180-day follow-up period to determine which approach may better reduce treatment failure and improve patient care while considering antimicrobial resistance concerns. Participants will be randomly assigned to one of two groups: the standard care group, where antibiotic type and duration are determined by their clinician, or the fixed extended-duration group, which receives antibiotics for a set 28-day period. The study includes a total of 1166 adult patients recruited from intensive care units and hospital wards across approximately 30 NHS trust hospitals. The treatment period is followed by monitoring up to 180 days after randomization. During the study, patients or their personal consultees will complete quality of life questionnaires at baseline and at 30, 60, and 180 days post-randomization. They will also provide information about antibiotic use and healthcare resource utilization. Researchers will collect hospital records on admissions, relapses, and further infections. The main outcome measured is treatment failure within 180 days of randomization, with safety and effectiveness assessed throughout the follow-up period.

Researchers are investigating the use of Magnetic Resonance Tumour Regression Grade (mrTRG) as a new imaging biomarker to guide treatment decisions in patients with locally advanced rectal cancer. This phase III trial in the UK is unique in offering a 'watch and wait' approach for patients who respond well to pre-operative treatment, potentially avoiding surgery and preserving quality of life. The study aims to validate mrTRG to differentiate between good and poor responders to radiotherapy and help tailor ongoing treatment and surveillance accordingly. Participants will be randomly assigned to one of two groups. The control group will receive standard management based on national guidelines and clinical assessments after treatment, including routine MRI scans without mrTRG reporting. The intervention group will have post-treatment MRI scans evaluated by specially trained radiologists to assess mrTRG grades. Patients classified as good responders (mrTRG 1 or 2) will be offered a watch and wait approach to avoid surgery, while poor responders (mrTRG 3 to 5) will have their cases reviewed by a local colorectal multidisciplinary team for further treatment planning. During the study, all participants will undergo routine MRI scans following standardized protocols and complete quality of life questionnaires at registration, 3 years, and 5 years. Researchers will monitor outcomes for up to five years, focusing on whether surgery can be safely avoided in good responders and tracking long-term effects on health and survival. The study does not mandate specific chemotherapy or investigational treatments, allowing local teams to decide additional therapy as needed.

Researchers are evaluating the effects of two different default dialysate sodium concentrations, 137 mmol/l and 140 mmol/l, on major cardiovascular events and death in adults receiving maintenance haemodialysis. This pragmatic, cluster-randomised, open-label study takes place in real-world dialysis sites and aims to compare the outcomes associated with these sodium levels over an extended period. The study focuses on patients with end-stage kidney disease undergoing regular haemodialysis treatment. Dialysis sites are randomly assigned to use either a default dialysate sodium concentration of 137 mmol/l or 140 mmol/l for at least 90% of dialysis sessions at that site. All other care practices continue as usual based on local standards. The study plans to recruit sites over 5 to 7 years, with individual follow-up lasting roughly 2 to 5 years. Site participation requires consent, while individual patient consent may be waived or offered an opt-out option. Participants will be monitored for major cardiovascular events and death, with the primary outcome measuring the time until the first such event occurs. Data collection methods are implemented across participating dialysis units, focusing only on in-center or satellite dialysis patients where applicable. The study's duration depends on the occurrence of endpoints, with an average follow-up of about 5 years anticipated per participant.

Researchers are investigating treatments for patients with localized renal cell carcinoma (RCC) who have undergone nephrectomy, focusing on those at high or intermediate risk of the cancer returning. The study evaluates whether durvalumab alone or combined with tremelimumab can improve disease-free survival or overall survival compared to the current standard of care, which is active monitoring. This phase III multi-arm, multi-stage randomized controlled trial includes patients with specific risk scores, and recruitment of intermediate risk patients will be limited based on time and accrual targets. Participants will be randomly assigned to receive either durvalumab alone, the combination of durvalumab and tremelimumab, or active monitoring. The drugs are given via controlled infusion through a pump into a vein. The trial includes a screening phase and treatment period, with careful monitoring of patients' disease status and side effects throughout the study. During the study, participants will undergo clinical and radiological assessments, including post-operative scans and laboratory tests like blood counts and ECGs. Researchers will track disease-free survival and overall survival over several years, including specific time points up to 20.5 years for some comparisons. Participants will also provide tissue and blood samples for future research. Safety and treatment effects will be closely monitored to understand how the therapies impact long-term outcomes.

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.