Darlington

Researchers are evaluating the use of circulating tumour DNA ctDNA analysis to detect early molecular relapse in patients with estrogen receptor positive ER and HER2 negative breast cancer who are undergoing adjuvant endocrine therapy. This trial aims to determine if treatment with palbociclib plus fulvestrant can delay or prevent relapse in patients who show positive ctDNA results. The study is a Phase 2, multi-centre, randomized, open-label trial focusing on high-risk patients with early-stage breast cancer. The trial has two main phases a surveillance phase and a treatment phase. During the surveillance phase, patients receive ctDNA testing every three months for up to three years to monitor for molecular relapse. If ctDNA is detected without visible disease on imaging, patients enter the treatment phase, where they are randomly assigned to receive either standard endocrine therapy or a combination of palbociclib and fulvestrant for up to 24 months. Palbociclib is taken orally daily for 21 days of each 28-day cycle, while fulvestrant is given as intramuscular injections on specific days of each cycle. Imaging is performed every six months to check for overt disease. Participants undergo regular blood tests for ctDNA monitoring during the surveillance phase and receive clinical assessments, imaging scans, and quality of life questionnaires during the treatment phase. Researchers measure the incidence of positive ctDNA results, relapse-free survival, and monitor adverse events. The total follow-up for relapse-free survival extends up to 60 months from randomization, while safety and quality of life are assessed up to 24 months. If macroscopic disease appears, participants stop trial treatment and receive standard care outside the study.

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 multi-centre observational study to better understand giant cell arteritis GCA and polymyalgia rheumatica PMR, conditions mainly affecting people over 50 years old. The study aims to identify genetic factors that influence susceptibility to these diseases to provide new insights into how they develop. It includes both retrospective participants with confirmed diagnoses and prospective participants suspected of having these conditions, with some patients also enrolled in a registry monitoring tocilizumab treatment for relapsing or refractory GCA. The study collects detailed clinical, imaging, and molecular data, including genetic and proteomic analyses, from participants to characterize disease subtypes and impacts. Researchers also assess quality of life through patient-reported outcomes and track long-term prognosis by linking to health records. The study explores environmental factors and co-existing conditions to improve diagnosis, prognosis, and monitoring of disease activity, especially for patients receiving synthetic or biological disease-modifying anti-rheumatic drugs. Participants provide information during baseline assessments, including blood and urine samples for analysis, and complete questionnaires about their symptoms and quality of life. Follow-up occurs through health record review over an average of one year to evaluate diagnosis and disease outcomes. The primary measure is genetic susceptibility, with secondary outcomes focusing on disease characteristics, life impact, diagnosis, and disease activity. The study is sponsored by the University of Leeds and started in 2005, continuing through 2028.

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 effects of vicadrostat combined with empagliflozin in adults who have type 2 diabetes, high blood pressure, and cardiovascular disease but no history of heart failure. The study aims to assess whether this combination can help reduce cardiovascular risks compared to a placebo with empagliflozin. This Phase III trial involves adults with these conditions who are already receiving treatment for them. Participants are randomly assigned to one of two groups. One group takes vicadrostat and empagliflozin tablets daily, while the other group takes placebo tablets that look like vicadrostat but have no active medicine, alongside empagliflozin. Treatment lasts from two and a half years up to four years and three months. All participants continue their usual medications for diabetes, blood pressure, and heart disease during the study. Throughout the study, lasting up to four years and three months, participants visit the study site regularly for health checks and blood samples. Doctors monitor cardiovascular events and any side effects experienced. The main outcome measured is the time until the first cardiovascular death or heart failure event. Other health indicators like blood pressure and kidney function are also tracked to understand the effects of the treatment combination.

Researchers are evaluating the long-term effects of lidocaine infusions given during and after surgery to reduce moderate or severe chronic post-surgical pain in adult women undergoing elective breast cancer surgery. This large, international, randomized, double-blind trial aims to detect a meaningful reduction in chronic pain one year after surgery and also assesses safety, pain relief, opioid use, nerve-related pain symptoms, psychological health, and quality of life. Participants receive either a lidocaine infusion starting with an intravenous bolus after anesthesia induction, continuing with an intraoperative intravenous infusion, and followed by a post-operative subcutaneous infusion for up to 24 hours. The lidocaine dosing is adjusted by lean body weight with a cap, while the comparison group receives a saline placebo infusion following the same schedule. Day-case surgeries receive only the intraoperative treatments without the post-operative infusion. During the trial, participants will be monitored for pain severity, opioid consumption, nerve-related symptoms, psychological distress, physical functioning, quality of life, safety events, and health care costs up to one year after surgery. The primary outcome is the incidence of moderate or severe chronic post-surgical pain reported at one year. Assessments include patient-reported outcomes, pain scores at 24 hours postoperatively, and opioid use at various timepoints. The total participation duration extends up to one year after surgery.

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.

This research is investigating the use of Implantable Cardioverter-Defibrillators ICDs in adults diagnosed with heart failure caused by Non-Ischemic Cardiomyopathy NICM, a condition where heart failure is not due to blocked arteries. The study aims to compare the all-cause mortality rates between patients who receive an ICD and those who do not, over a period of 36 months and extending up to 10 years. This trial addresses ongoing questions about whether ICDs benefit patients with NICM, especially given recent findings that many patients with ICDs do not experience serious heart rhythm problems. Participants are randomly assigned to one of two groups one group will have an ICD or Cardiac Resynchronisation Therapy Defibrillator CRTD implanted, which are devices designed to detect and correct dangerous heart rhythms. The other group will not receive an ICD but may have an Implantable Loop Recorder or a Cardiac Resynchronisation Therapy Pacemaker CRTP, alongside their usual medical care. The study will monitor both groups to determine if ICD implantation improves survival compared to no ICD over the study period. Throughout the trial, participants will be regularly evaluated with health assessments including quality of life questionnaires and monitoring of heart-related events such as hospitalizations and arrhythmias. Researchers will track outcomes like survival percentage, heart rhythm events, and device-related procedures over 3 years, with some outcomes also measured at 5 and 10 years. The study includes close observation of safety and effectiveness, with participants followed to understand long-term impacts of ICD therapy in this patient group.

Depression and anxiety are common mental health issues affecting many adults. This trial evaluates an artificial intelligence tool called StratCare, designed to help the NHS Talking Therapies services offer the most suitable treatment for each patient. StratCare guides therapists through a brief assessment to recommend either brief or intensive therapy, aiming to improve recovery rates compared to the usual stepped care model. Participants will be adults with depression symptoms seeking treatment from NHS Talking Therapies services. Half of the participants will have their treatment guided by the StratCare app, which uses patient data and an algorithm to recommend low- or high-intensity therapy. The other half will follow the usual stepped care approach, where patients typically start with brief treatments and move to intensive therapy if needed. Treatments include up to eight sessions of low-intensity guided self-help or up to 20 sessions of high-intensity psychological therapy. During the study, participants will undergo standard clinical assessments, with data collected through the StratCare app, online or paper questionnaires, and telephone or video calls. Researchers will measure depressive symptoms using the Patient Health Questionnaire PHQ-9 at 12 months, along with anxiety, quality of life, and resource use at 6, 12, and 18 months. The study will also include interviews with therapists and participants to understand experiences with the AI-guided treatment process. The total participation duration spans at least 18 months with regular follow-ups.