Bolton

Researchers are evaluating the effects of tirzepatide compared with standard care in adults living with obesity who do not have diabetes. This phase 4 study aims to assess weight loss and the occurrence of type 2 diabetes over a long period in a real-world setting. Participants must have obesity and at least one weight-related health condition to join the study. Participants will receive either tirzepatide, given once weekly by injection under the skin, or continue with standard care as determined by their healthcare providers. The study is designed to reflect real-life treatment and monitoring situations to understand how tirzepatide works outside of tightly controlled clinical trials. The study lasts about 260 weeks, during which participants will be regularly monitored for changes in body weight and the development of type 2 diabetes. Measurements will be taken at the start and throughout the study to track weight changes. Researchers will also observe safety and overall health during this extended follow-up period.

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 evaluating the safety and effectiveness of whole-body hypothermia treatment in newborn babies diagnosed with mild hypoxic ischaemic encephalopathy (HIE). This phase III randomized controlled trial aims to determine whether cooling babies to 33.57b0C within six hours of birth for 72 hours improves cognitive development at two years of age compared to maintaining normal body temperature (normothermia). The study also assesses the cost-effectiveness of cooling therapy to help guide national and international treatment guidelines and standardize care across the NHS. Babies born at or after 36 weeks with specific signs of birth asphyxia or acidosis are randomly assigned to either whole-body hypothermia or targeted normothermia groups. The hypothermia group will have their body temperature lowered and maintained at 33.57b0C using a cooling machine for 72 hours in a neonatal intensive care unit. The normothermia group will have their temperature maintained at 377b0C with treatment for any fever using standard protocols. If babies in the normothermia group develop seizures and worsen to moderate HIE, they may receive cooling treatment as part of clinical care. Conventional MRI scans will be performed before discharge. Participants will be followed up at 24 months of age (7 months) using the Bayley Scales of Infant and Toddler Development IV to measure cognitive, language, and motor skills. Additional neurological exams, including assessments for cerebral palsy, vision, and hearing, will be conducted. Parents will complete questionnaires about their child's development. Researchers will collect detailed clinical data from birth through follow-up to evaluate safety and developmental outcomes. Babies who die or cannot complete assessments due to severe disability will be assigned specific scores to reflect outcomes.

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.

This research focuses on evaluating the use of intravenously administered fosfomycin to treat severely infected patients across Europe. It includes those with serious infections such as osteomyelitis, complicated urinary tract infections, nosocomial lower respiratory tract infections, bacterial meningitis and central nervous system infections, bacteraemia or sepsis, skin and soft tissue infections, endocarditis, and other infections as permitted by national guidelines. The study is prospective, multicenter, non-interventional, and aims to document both the effectiveness and safety of this treatment. Patients receive fosfomycin treatment according to the national Summary of Product Characteristics (SmPC) guidelines for fosfomycin intravenous use. The study does not involve comparing treatment groups or altering standard care but observes patients receiving fosfomycin in routine clinical settings. There are no specific dosing schedules or additional interventions imposed by the study protocol. During the study, participants are monitored until the end of treatment, which may last up to six months after starting fosfomycin. Researchers evaluate clinical success by assessing whether patients achieve clinical cure or improvement. Safety and outcomes are recorded through clinical observations, with the goal of better understanding fosfomycin's role in treating severe infections.

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 evaluating if using additional liver diffusion weighted MRI (DW-MRI) scans at diagnosis can find more synchronous liver metastases than CT scans alone in patients with high risk colorectal cancer. This phase II multicenter study focuses on patients with advanced primary colorectal tumors who have no evidence of liver metastases on CT scans. The goal is to improve detection and management of liver metastases by sharing MRI findings with multidisciplinary teams for treatment decisions. Participants will undergo additional breath hold T1, T2, and DW-MRI liver scans without intravenous contrast every six months for three years after surgery. Any liver metastases detected on these scans will be reviewed by the local multidisciplinary team and treated following local protocols. This ongoing monitoring aims to identify metastases early and guide appropriate therapy. During the study, participants will have regular imaging assessments and clinical evaluations as part of their post-surgery surveillance. The researchers will measure the presence of liver metastases through these MRIs and track treatment responses. Findings will be discussed in multidisciplinary team meetings, and participants will be followed for five years after the last recruitment to assess long-term outcomes and management of liver metastases.