Dartford

Researchers are evaluating the safety and effectiveness of whole-body hypothermia for newborn babies with mild hypoxic ischaemic encephalopathy. This phase III randomised controlled trial aims to determine whether cooling the whole body to 33.5.5C within six hours after birth and continuing for 72 hours improves cognitive development at around two years of age compared with maintaining normal body temperature. The study also seeks to assess the economic value of cooling therapy for mild encephalopathy within the healthcare system. Babies born at or after 36 weeks with signs of birth asphyxia or acidosis will be randomly assigned to receive either whole-body hypothermia or targeted normothermia. Cooling will be applied using a servo-controlled machine in neonatal intensive care units, maintaining a rectal temperature of about 33.5C for 72 hours. The control group will have their body temperature kept at normal levels 37C for the first 80 hours, with any fever carefully treated. Babies born at non-cooling centers will be transferred to specialized units for treatment. During the study, participants will undergo brain monitoring, MRI scans before discharge, and follow-up developmental assessments at 24 months using the Bayley Scales of Infant and Toddler Development IV. Additional evaluations will include neurological exams, motor function assessments, vision and hearing tests, and parent-completed questionnaires. Researchers will collect detailed clinical data from birth through hospital stay, aiming to compare cognitive outcomes and safety measures between the two groups over the study period.

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.

Researchers are evaluating the use of two types of MRI scans and two biopsy methods to improve prostate cancer diagnosis. The study focuses on whether biparametric MRI bpMRI, which is shorter and does not use contrast dye, can be an alternative to the longer multiparametric MRI mpMRI that uses gadolinium contrast. It also compares image-fusion targeted biopsy, which overlays MRI and ultrasound images during biopsy, with visual-registration targeted biopsy, where biopsy locations are chosen by looking at MRI images separately. Participants first receive either the mpMRI or bpMRI scan. If the MRI suggests cancer, the clinical team decides if a biopsy is needed. Those advised for biopsy undergo either a visual-registration targeted biopsy or an image-fusion targeted biopsy. Both biopsy methods include taking systematic tissue samples to check for cancer. The study does not blind participants or doctors to the MRI or biopsy type used. During the study, participants undergo MRI scans and possibly biopsies based on clinical advice. Researchers collect data on how many clinically significant prostate cancers are detected within 12 weeks of enrollment. They also assess any adverse events related to MRI and biopsy procedures, patient-reported outcomes, and accuracy of cancer detection using different scoring systems. The total duration for outcome assessment is up to 12 weeks after joining the study.

Researchers are evaluating whether regular MRI scans can better detect progression in patients on active surveillance for low to medium risk prostate cancer compared to the current standard care defined by NICE. The study aims to see if MRI scans reduce the number of PSA tests, biopsies, and clinic visits over five years while improving cancer progression detection. This trial involves patients who have chosen active surveillance and have a histological diagnosis of localized prostate cancer. Participants are randomly assigned to one of two groups. The standard care group will have PSA tests every 3 months in the first year, then every 6 months with annual rectal exams when clinically indicated, and an MRI at 12 months if not done at diagnosis. Biopsies occur if PSA or rectal exams indicate changes. The intervention group will have PSA tests every 6 months and regular MRI scans annually for patients with visible lesions or medium risk cancer, or in years 1, 3, and 5 for others. Targeted biopsies are performed if MRI PRECISE scores are 4 or higher. The MRI scans are biparametric and do not use gadolinium contrast. Participants will be followed for five years with regular PSA tests, MRI scans, biopsies when indicated, and clinical assessments. Researchers will monitor biopsy and staging results, cost-effectiveness, adverse events related to MRI and biopsies, treatment decisions, compliance, and quality of life using questionnaires on prostate symptoms, anxiety, and general health. The trial is not blinded and aims to provide evidence to improve active surveillance protocols while reducing invasive procedures and healthcare costs.

Researchers are studying patients with chronic lymphocytic leukaemia CLL who have been treated with acalabrutinib in the United Kingdom. This observational study aims to describe the characteristics and real-world clinical outcomes of these patients, especially those who started acalabrutinib treatment as part of the UK Early Access Programme. The study seeks to provide UK-specific data on how patients respond to and tolerate acalabrutinib in typical clinical settings. The study involves reviewing clinical records of treatment-naefve CLL patients who began acalabrutinib between April 1, 2020, and April 1, 2021. The focus is on patients treated in the first-line setting with acalabrutinib under the Early Access Programme. This non-interventional study does not involve new treatments but collects and analyzes existing data to estimate progression-free survival, overall survival, response rates, treatment patterns, and healthcare resource use. Participants medical information will be gathered from their clinical records following local laws. Researchers will track outcomes such as progression-free survival at various time points up to 60 months, overall survival, response rates, and treatment interruptions. The study design allows for long-term observation of how patients fare with acalabrutinib, providing valuable real-world evidence. The study is expected to continue through April 2027.

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 evaluating treatments for community-acquired pneumonia CAP, especially in patients admitted to intensive care units ICUs. This trial also adapts to study treatments for respiratory pandemics like COVID-19. The goal is to determine which treatment strategies improve outcomes for patients with severe pneumonia, using a flexible, ongoing approach that can test multiple therapies simultaneously and update as new information becomes available. Participants receive different treatment strategies based on random assignment to study groups. Treatments include various antibiotics, steroids, antivirals, immune modulators, anticoagulation methods, and ventilation strategies. Some treatment options have been closed to recruitment, reflecting the trials adaptive nature. The trial includes several domains targeting specific infections such as influenza and COVID-19, with dosing and duration guided by clinical practice and local guidelines. During the study, participants are monitored closely with assessments including survival up to 90 days, days alive without organ support in ICU, ICU and hospital length of stay, ventilator-free days, organ failure-free days, and quality of life up to 6 months. Researchers collect detailed data on patient outcomes, organ support needs, and hospital discharge status. The study runs until February 2028, with ongoing evaluation to improve pneumonia treatment strategies in ICU settings and during respiratory pandemics.

Researchers are investigating the use of short-term androgen deprivation therapy with apalutamide Erleada in men on active surveillance for early prostate cancer. This phase 2, randomized, multicenter, double-blind, placebo-controlled trial aims to evaluate the effects of apalutamide on tumor progression in men at risk while under active surveillance. The study is sponsored by Cambridge University Hospitals NHS Foundation Trust and focuses on men with MRI-detectable prostate lesions and specific biopsy findings who are managing their cancer without immediate treatment. Participants will be randomly assigned to one of three groups one group will receive apalutamide 240 mg daily for up to 6 months another group will receive apalutamide 240 mg daily for 3 months followed by placebo for 3 months and the third group will receive placebo daily for 6 months. The study uses tablets taken orally and includes a quadruple-blind design to compare these treatments. The treatment phase is followed by a monitoring period to assess outcomes. During the trial, participants will undergo MRI scans to measure tumor volume 12 months after treatment ends. Researchers will also collect patient-reported outcomes on quality of life and track any adverse events from consent through 30 to 45 days post-treatment. Longer-term outcomes include progression rates over 3 years after treatment completion. The study involves regular clinical and laboratory assessments to monitor safety and effectiveness, with overall participation lasting several years to capture these measures.