Dartford

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 investigating the effects of a medicine called BI 690517 in combination with empagliflozin for adults with chronic kidney disease who are at risk of their condition worsening. This study includes people both with and without type 2 diabetes and those already taking certain kidney-related medicines like ACE inhibitors or angiotensin receptor blockers. The goal is to understand if adding BI 690517 helps protect kidney function and reduces risks related to kidney failure and heart problems. This is a Phase 3 clinical trial conducted over about 3 to 4 years. The study has two parts. First, participants receive either empagliflozin or a placebo similar to BI 690517 for at least six weeks, while continuing other indicated treatments like ACE inhibitors or ARBs. In the second part, participants are randomly assigned to take either BI 690517 tablets or placebo tablets once daily alongside empagliflozin for the rest of the study. The placebo tablets look like BI 690517 but contain no active medicine. Participants have regular visits to the study site, about four times in the first six months, then every six months afterward. During these visits, doctors monitor kidney function, heart health, blood pressure, weight, and any side effects. Blood and urine samples are taken to track health changes. The main outcomes measured are the time until worsening kidney disease, hospitalization for heart failure, or cardiovascular death. The study ends when a certain number of these events have occurred.

Researchers are evaluating the use of biparametric MRI (bpMRI) and image-fusion targeted biopsies to detect prostate cancer in men at risk. The study aims to determine if bpMRI can be recommended as an alternative to the longer multiparametric MRI (mpMRI) for identifying clinically significant prostate cancers. It also compares image-fusion targeted biopsy with visual-registration targeted biopsy to see which method better detects significant prostate cancer in patients with suspicious MRI findings. Participants will undergo one of two types of MRI scans: a longer 30-40 minute MRI that uses a contrast dye called gadolinium (commonly used in the NHS), or a shorter MRI without contrast. If the MRI shows suspicious areas, participants may then have a prostate biopsy. Biopsies are performed either by visual registration, where the biopsy needle placement is guided by the operator’s judgment using MRI and ultrasound images, or by image fusion, where MRI images are overlaid on live ultrasound using software to guide the biopsy needle more precisely. During the study, patient scans and biopsy results will be closely monitored and analyzed to measure how many clinically significant cancers are detected within 12 weeks of enrollment. Researchers will collect MRI images, perform biopsies if indicated, and evaluate the biopsy samples under a microscope. The study includes safety monitoring and aims to inform future NHS practices for prostate cancer diagnosis. Male participants aged 18 and older who are referred for prostate MRI due to abnormal exams or elevated PSA levels are eligible to join.

Researchers are evaluating whether regular MRI scans can better detect cancer progression in patients on active surveillance for low to medium risk prostate cancer compared to the current standard care recommended by NICE. This study focuses on patients who have chosen active surveillance, as immediate treatment may not improve survival but can cause significant side effects. The trial aims to improve detection of progression over 5 years with fewer biopsies, PSA tests, and clinic visits, potentially reducing anxiety and healthcare costs. Participants will be randomly assigned to either regular MRI scans or the current standard of care. Those in the MRI group will have PSA tests every 6 months and MRI scans annually if they have visible lesions or medium risk cancer. Other patients will have PSA every 6 months and MRI scans in years 1, 3, and 5. Targeted biopsies will be done if MRI shows signs of progression. The standard care group will follow NICE guidelines with regular PSA tests, rectal exams, and biopsies as indicated. During the study, patients will undergo diagnostic MRI scans and biopsies as needed, with monitoring including PSA testing and clinical examinations. The main outcomes measured are biopsy results and cancer staging over 5 years. The study is not blinded and stratifies patients by MRI lesion visibility, cancer grade, and time since diagnosis to ensure balanced groups. The total duration of follow-up is 5 years to assess progression detection and resource use.

Researchers are studying patients with chronic lymphocytic leukaemia (CLL) who are treated with acalabrutinib in the United Kingdom. This observational research looks back at real-world clinical outcomes for patients who started acalabrutinib through the UK's Early Access Programme (EAP). The study aims to describe characteristics of these patients and estimate progression-free survival, overall survival, response rates, treatment patterns, and healthcare resource use. The study focuses on patients who began first-line treatment with acalabrutinib between April 1, 2020, and April 1, 2021. It collects clinical data from patients' medical records in accordance with local laws. This non-interventional study does not assign treatments but observes outcomes from the use of acalabrutinib as provided in routine care. Participants' medical records will be reviewed to assess progression-free survival at multiple time points up to five years, along with other outcomes such as overall survival and treatment responses. The study also evaluates healthcare resource use and post-progression treatments. By gathering this data, researchers aim to provide useful real-world evidence on acalabrutinib's use in the UK for patients with CLL over the course of their treatment.

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 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.

Researchers are evaluating the effectiveness and safety of ONCOFID-P-B, a paclitaxel-hyaluronic acid conjugate, administered directly into the bladder of adult patients with carcinoma in situ (CIS) of the bladder who have not responded to BCG therapy and are unwilling or unable to undergo radical cystectomy. This phase III, single-arm, international study focuses on patients with histologically and cytologically confirmed CIS, with or without associated Ta-T1 papillary disease, aiming to assess the complete response rate at any time during the study. Participants will receive ONCOFID-P-B once a week for 12 weeks during the induction phase. Patients achieving a complete response proceed to the maintenance phase, receiving monthly intravesical instillations for 12 months or until disease recurrence or progression. Those with residual CIS after induction may undergo a re-induction course. Tumor response is assessed by cystoscopy, cytology, and biopsy at specific time points including the end of induction, re-induction, and safety follow-up visits. Throughout the study, patients will have scheduled evaluations including cystoscopy and cytology every three months for two years, then every six months for an additional two years. Biopsies are performed when cystoscopy or cytology results are positive, with random biopsies at 6, 12, and 18 months for responders. Patients who do not achieve complete response discontinue treatment but continue follow-up for up to 48 months or until new therapy begins. The study monitors efficacy, safety, and long-term outcomes over several years.

Researchers are evaluating the use of short-term androgen deprivation therapy with apalutamide (Erleada) in men who are on active surveillance for early prostate cancer. This phase 2, randomized, multicenter, double-blind, placebo-controlled trial aims to study whether apalutamide can affect tumor progression in this patient group. The study focuses on men with prostate cancer who meet specific clinical and imaging criteria and are under active surveillance rather than immediate treatment. Participants will be assigned to receive either apalutamide oral tablets or a matching placebo. Apalutamide is a selective androgen receptor inhibitor that targets the prostate cancer cells by binding to their androgen receptors. Treatment duration and dosing schedules are determined by the study protocol, and participants are monitored closely throughout the trial. The study also includes safety monitoring and follow-up to assess the effects of treatment over time. During the trial, men will undergo regular assessments including MRI scans to measure tumor volume 12 months after the end of treatment. Clinical laboratory tests, prostate imaging, and biopsies are part of the evaluation process. Researchers will collect data on tumor changes, safety, and tolerability of the therapy. The total duration of participation depends on the study timeline including treatment and follow-up periods, with detailed monitoring to support study outcomes and participant safety.