Hereford

The purpose of this study is to evaluate the efficacy of icotrokinra compared to placebo in biologic-experienced participants with active psoriatic arthritis (PsA) by assessing the reduction in signs and symptoms of PsA.

Background: The presence of cancer in the axillary lymph nodes on needle biopsy in patients with early stage breast cancer before neoadjuvant chemotherapy (NACT) has been the determinant of the need for axillary treatment (in the form of axillary lymph node dissection (ALND) or axillary radiotherapy (ART)) after completion of NACT. Treatment to the axilla damages lymphatic drainage from the arm and patients can subsequently develop lymphoedema, restricted shoulder movement, pain, numbness, and other sensory problems. As more effective chemotherapy is now available that results in complete eradication of cancer in the axilla in around 40 to 70% of patients, extensive axillary treatment might no longer be necessary in patients with no evidence of residual nodal disease. Aim: To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy, who after NACT have no residual cancer in the lymph nodes on sentinel node biopsy, is non-inferior to axillary treatment in terms of disease free survival (DFS) and results in reduced risk of lymphoedema at 5 years. Methods: Study design: A pragmatic, phase 3, open, randomised, multicentre trial and embedded economic evaluation in which participants will be randomised in a 1:1 ratio. Study population: T1-3N1M0 breast cancer patients aged 18 years or older, with needle biopsy proven nodal metastases, who after NACT have no residual cancer in the lymph nodes on dual tracer sentinel node biopsy and removal of at least 3 lymph nodes (sentinel nodes and marked involved node). Intervention: All participants will receive human epidermal growth factor receptor 2 (HER2)-targeted treatment, endocrine therapy and radiotherapy to breast or chest wall, if indicated according to local guidelines. Patients in the intervention group will not receive further axillary treatment (ALND or ART), whereas those receiving standard care will receive axillary treatment (ALND or ART) as per local guidelines. Follow-up is annually for at least 5 years. Outcomes: The co-primary outcomes are disease free survival(DFS) and self-reported lymphoedema defined as 'yes' to the two questions participants will be asked - 'arm heaviness during the past year' and 'arm swelling now' from the Lymphoedema and Breast Cancer Questionnaire at 5 years. Secondary outcomes: arm function assessed by the QuickDASH (disabilities of the arm, shoulder and hand) questionnaire; health related quality of life assessed using euroqol EQ-5D-5L; axillary recurrence free interval (ARFI); local recurrence; regional (nodal) recurrence; distant metastasis; overall survival; contralateral breast cancer; non-breast malignancy; costs; quality adjusted life years (QALYs) and cost-effectiveness. Sample size: A sample size of 1900 patients would have the ability to demonstrate a 3.5% non-inferiority margin with a 5% 1-sided significance level and 85% power, allowing for 7% non-collection of primary outcome data assuming a 90% 5-year disease free survival rate in the control arm. It would also be able to detect at least a 5% difference in proportion of patients with lymphoedema with 90% power, a 5% 2-sided significance level and allowing for 25% non-collection of primary outcome data over 5 years. Analysis plan: All analyses will be carried out on an intention-to-treat basis to preserve randomisation, avoid bias from exclusions and preserve statistical power. Time to event outcomes, including disease free survival and axillary recurrence free interval, will be assessed using Kaplan-Meier curves and compared using Cox proportional hazards models. The proportion of patients experiencing lymphoedema at 5 years will be compared across trial arms using a chi-squared test and a logistic regression model used to adjust for stratification variables. Arm morbidity and health related quality of life will be scored using the appropriate manuals and assessed using a longitudinal mixed model regression analysis if model assumptions valid or a standardised area-under-the-curve analysis. For economic evaluation, incremental cost per QALY gained at 5 years will be estimated. Timelines for delivery: Total project duration is 120 months based on 6 months for set up; 60 months recruitment period (including an 18 months internal pilot phase); and 54 months for follow up, analysis, writing up and dissemination.

This study is open to adults with chronic kidney disease at risk of progression. People with and without type 2 diabetes can take part in this study. The study is open to people who take other medicines called angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). People who already take empagliflozin or any other sodium-glucose cotransporter-2 inhibitor (SGLT2i) can also join. The study is also open to people who currently do not take any of these treatments. The purpose of this study is to find out whether a medicine called BI 690517 helps people with chronic kidney disease when taken in combination with a study medicine called empagliflozin. Worsening of kidney function increases the risk for kidney failure, cardiovascular disease, and heart disease. This study has 2 parts. In the first part, participants get empagliflozin or placebo matching BI 690517 for at least 6 weeks. Participants continue taking ACEi or ARB throughout the study if such treatments are indicated. In the second part, participants are divided into 2 groups by chance. One group takes BI 690517 tablets and the other group takes placebo tablets. Placebo tablets look like BI 690517 tablets but do not contain any medicine. Participants take 1 tablet once a day in addition to empagliflozin for the duration of the study. The doctors document when participants experience worsening of their kidney disease, go to hospital due to heart failure, or die of cardiovascular problems during the study. The time to these events is compared between the 2 treatment groups to see whether the treatment works. The study continues until the required number of events have occurred which is about 3 to 4 years. During this time, participants visit the study site about 4 times within the first 6 months. Then they visit the study site every 6 months. At the visits, doctors regularly check participants' health, take blood and urine samples, measure blood pressure and weight, check kidney function, and take note of any unwanted effects.

Community-acquired pneumonia (CAP) that is of sufficient severity to require admission to an intensive care unit (ICU) is associated with substantial mortality. Patients with pneumonia who are being treated in an ICU will receive therapy that consists of many different treatments, as many as 20 or 30. These treatments act together to treat both the infection and its effects on the body. When treating a patient, doctors choose from many different treatments, most of which are known or believed to be safe and effective. However, doctors don't always know which treatment option is the better one, as individuals or groups of individuals may respond differently. This study aims to help doctors understand which treatments work best. This clinical study has been designed in a way that allows the information from patients already in the study to help new patients joining the study. Most studies aren't able to do that. REMAP-CAP has been designed to: * Evaluate multiple treatment strategies, at the same time, in the same patient. * Reach platform conclusions when sufficient data is accrued, rather than when a pre-specified sample size is reached * Utilise data that is already accrued to increase the likelihood that patients within the trial are randomised to treatments that are more likely to be beneficial * New questions can be substituted into the trial as initial questions are answered, meaning that the trial can be perpetual or open-ended * Interactions between interventions in different domains can be evaluated It is reasonable to presume that any pandemic respiratory infection of major significance to public health will manifest as life-threatening respiratory infection including Severe Acute Respiratory illness and severe Community Acquired Pneumonia (CAP) with concomitant admission to hospital, and for some patients, admission to an Intensive Care Unit (ICU). Previous pandemics and more localized outbreaks of respiratory emerging infections have resulted in severe CAP and ICU admission. Previous pandemics and outbreaks of emerging infectious diseases have outlined the urgent need for evidence, preferably from Randomized Controlled Trials (RCTs), to guide best treatment. However, there are substantial challenges associated with being able to organize such trials when the time of onset of a pandemic and its exact nature are unpredictable. As an adaptive platform trial that enrolls patients during the interpandemic period, REMAP-CAP is ideally positioned to adapt, in the event of a respiratory pandemic, to evaluate existing treatments as well as novel approaches.

Patients are recruited in the platform for the research purpose of 5 downstream projects. For more information, please have a look at the "Groups and cohorts" section.