Frimley

This is a Phase 3 multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of subcutaneous administration of navenibart in adult and adolescent participants with type 1 or type 2 hereditary angioedema (HAE). The goal of this clinical trial is to evaluate the efficacy and safety of navenibart compared to placebo in preventing HAE attacks in participants with HAE.

This study is open to adults 18 and older with an eye condition called diabetic macular edema. People are required to have a specific type of diabetic macular edema called centre-involved diabetic macular edema (CI-DME) to take part. The purpose of this study is to find out whether a medicine called BI 1815368 improves sight in people with CI-DME and to find the most suitable dose. This study has 2 parts. In the first part, participants are put into 2 groups of equal size randomly, which means by chance. One group takes BI 1815368 tablets and the other group takes placebo tablets. Placebo tablets look like BI 1815368 tablets but do not contain any medicine. In the second part, participants are put into 4 groups of equal size randomly. 3 groups take different daily doses of the study medicine, BI 1815368, while 1 group takes placebo. All participants take tablets twice a day for about 11 months. Participants are in the study for about 1 year. During this time, they visit the study site 16 times. At visits, doctors check the participant's vision and collect information on any health problems. They take detailed pictures of the eye. The changes over time are compared between the groups to see if the treatment works.

CALCIO is a multicentre, prospective, observational cohort study that will collect real world data on the use of intravascular Lithotripsy (IVL) with the Shockwave IVL system to disrupt calcified femoropopliteal and crural lesions in patients with chronic limb-threatening ischemia (CLTI). The primary objective of CALCIO is to understand the effectiveness of IVL in promoting wound healing and preventing amputation. The secondary objectives of CALCIO are to evaluate the immediate effectiveness of the treatment in restoring vessel patency as well as its safety and impact on patients' quality of life.

Giant cell arteritis (GCA), also known as temporal arteritis, is the most common form of primary systemic vasculitis, with up to 75,000 cases a year identified in the EU and US. It occurs almost exclusively in people over the age of 50 years and is considered to be a medical emergency. If not treated with high-dose glucocorticoids immediately, the thickening of the inflamed blood vessel wall can cause irreversible visual loss or stroke. GCA can lead to significant morbidity across a variety of systems, due to both the disease, and complications of treatment. Diagnosis may be confirmed with a temporal artery biopsy, imaging (e.g. USS/CT/MRA/PET-CR) or based on clinical signs (e.g. erythrocyte sedimentation rate) and symptoms (e.g. a new headache, jaw claudication, visual disturbances, temporal artery abnormality such as tenderness or decreased pulsation) . Polymyalgia rheumatica (PMR) is characterised by inflammatory limb-girdle pain with early morning stiffness, and a systemic inflammatory response demonstrated by elevated inflammatory markers. The UK GCA Consortium is a multi-centre observational study, the main arms of which recruit prospective (participants with suspected GCA) and retrospective cohorts (participants with confirmed GCA diagnosis). Analysis of data collected on these cohorts will help achieve the primary aim of finding genetic determinants of GCA and PMR susceptibility, in order to yield novel insights into disease pathogenesis. Secondary aims, and their associated analyses, are as follows: * Phenotype: characterising GCA and PMR subtypes, based on clinical features; imaging; cells; subcellular fractions and molecules in the circulation and/or arterial tissue; genetic/epigenetic/transcriptomic/proteomic or metabolomics factors, including next generation sequencing (whole exome sequencing) of selected cases. * Life impact: determining what aspects of the disease and treatments affect patients' quality of life, as assessed by patient-reported outcomes. * Long-term outcomes: characterising prognosis of GCA and PMR - both effects of the disease and its treatment - by longitudinal follow-up through electronic linkage to health records. * Exploratory analyses: exploring the potential role of environmental factors and co-morbidities on phenotype and outcomes. * Diagnosis, prognosis: improving diagnosis of GCA and PMR, and identifying factors that predict diagnosis, such as diagnostic clinical features, and prognostic and diagnostic biomarkers. * Disease activity: monitoring participants who commence a synthetic or biological disease-modifying anti-rheumatic drug (s/bDMARD). Finding a biomarker for GCA and PMR disease activity, which might be clinically useful in helping to optimise steroid and s/bDMARD treatments for individual patients.

This study is a multi-centre prospective observational cohort study recruiting patients with 5-30mm solid and part-solid pulmonary nodules that have been detected on CT chest scans performed as part of routine practice. The aim is to determine whether physician decision making with the AI-based LCP tool, generates clinical and health-economic benefits over the current standard of care of these patients.

This study is open to adults who are at least 18 years old and have: * A confirmed liver disease called non-alcoholic steatohepatitis (NASH) or * A confirmed liver disease called metabolic-associated steatohepatitis (MASH) * BMI of 27 kg/m2 or more or * 25 kg/m2 or more if the participant is Asian. People with a history of other chronic liver diseases or high alcohol intake cannot take part in this study. The purpose of this study is to find out whether a medicine called survodutide helps people with NASH or MASH improve their liver function. Participants are put into 2 groups randomly, which means by chance. 1 group gets survodutide and 1 group gets placebo. Placebo looks like survodutide but does not contain any medicine. Each participant has twice the chance of getting survodutide. Participants and doctors do not know who is in which group. Participants inject survodutide or placebo under their skin once a week. All participants regularly receive counselling to make changes to their diet and to exercise regularly. Participants are in the study for up to 4 and a half years. During this time, they visit the study site or have a remote visit by video call every 2, 4 or 6 weeks for about a 1 year and 5 months. After this time participants visit the trial site or have a remote visit every 3 months until the end of the study. The doctors check participants' health and take note of any unwanted effects. The participants' body weight is regularly measured. At some visits the liver parameters are measured using different imaging methods. The participants also fill in questionnaires about their symptoms. The results are compared between the groups to see whether the treatment works.

This study is open to adults who are at least 18 years old living with obesity and have: * a confirmed liver disease called non-alcoholic steatohepatitis (NASH)/metabolic associated steatohepatitis (MASH) and * moderate or advanced liver fibrosis People with a history of acute or chronic liver diseases other than MASH or chronic alcohol intake cannot take part in this study. The purpose of this study is to find out whether a medicine called survodutide helps people with MASH and moderate or advanced liver fibrosis improve their liver function. This study has 2 parts. The purpose of the first part of this study is to find out the effect of survodutide on MASH and liver fibrosis. The purpose of the second part is to find out how safe and effective survodutide is in improving liver function. Participants are put into 2 groups randomly, which means by chance. 1 group gets survodutide and 1 group gets placebo. Placebo looks like survodutide but does not contain any medicine. Each participant has twice the chance of getting survodutide. Participants and doctors do not know who is in which group. Participants inject survodutide or placebo under their skin once a week. The survodutide doses are slowly increased until the target dose is reached. All participants receive counselling to make changes to their diet and to exercise regularly. Participants are in the study for up to 7 years. During this time, they regularly visit the study site or have remote visits by video call. For about the first year of the study, participants have these visits every 2 weeks, increasing to every 4 weeks and then every 6 weeks. After being in the study for a little over a year participants will then alternate between visiting the study site or having a remote visit every 3 months until the end of the study. The doctors check participants' health and take note of any unwanted effects. The participants' body weight and effects on the stomach and intestines are regularly measured. At some visits the liver is measured using different imaging methods. At 2 or 3 visits doctors take a small sample of liver tissue (biopsy). The participants also fill in questionnaires about their symptoms and quality of life. The results are compared between the groups to see whether the treatment works.

Aim The aim of the current research is to explore whether volunteers can be trained to deliver exercise support to older adults across three different sized hospitals in different locations. Researchers will also explore if the intervention is accepted by patients, volunteers and staff and if it has any benefits on patients' health and functional outcomes (e.g., quality of life and muscle strength). Study Design This is a multicentre feasibility study using mixed methods (i.e., quantitative and qualitative measures) to explore the implementation of a volunteer-led physical activity intervention to older adults in hospital. The study will include three intervention sites and one control site. Feasibility studies are used to determine whether an intervention is appropriate for further evaluation, to determine sample sizes for controlled trials and to assess whether the ideas and findings can be shaped to be relevant and sustainable. Sample Size A sample size of 180 patients, 90 intervention (30 from each intervention site) and 90 from the control site, was chosen in line with previous sample size recommendations for feasibility studies of 24-50 participants. This sample size was considered an appropriate number that is pragmatic and achievable within the study timescale and resources available at each site. This research aims to recruit 15 volunteers at each site to provide sufficient cover to deliver the intervention. In a previous study (SoMoVe trial) 17 volunteers were recruited, 16 completed training and 12 were retained. Recruitment and Consent Older adults with an acute medical admission to four hospitals will be screened for eligibility by research nurses. Eligible patients will be introduced to the study by ward staff. Those who are interested in the study will be approached by the research team for further information and information sheets will be provided. Written informed consent will be obtained from all patients who agree to participate in the study. Volunteers will be invited by hospital voluntary services within each hospital site. The voluntary services team will send the interested volunteers details to the research team, who will then get in contact to complete informed consent. Inclusion and Exclusion Criteria Patients: The inclusion criteria are adults aged 65 years and above who are able to provide informed consent. Exclusion criteria are anyone with a severe cognitive impairment (MoCA less than 10), patients isolated for infection control reasons, and patients receiving end of life care. Volunteers: The inclusion criteria for volunteers are age 18 years and above, who have completed the generic clearance and training with the hospital voluntary services, who can provide written informed consent, and are able to communicate fluently enough in English. Fluent English is required to ensure the intervention content can be delivered clearly and thus safely to participants. Volunteers that are unable to safely complete the exercises included in the intervention will be excluded from the study. Intervention The exercises were developed based on clinical expertise from therapists and from our previous research of volunteer-led mobility interventions in hospital (SoMoVe study). Participants will be assessed by the therapy team who will prescribe tailored activity and then liaise with the mobility volunteers, who will deliver the intervention. Participants who can mobilise independently will be encouraged to perform walking exercises, progressing their walking distance over set markers in the hospital (e.g., to the end of the bed and back; to the doorway and back; to the toilet and back). Participants who require assistance in mobility will perform bed (e.g., hip abduction, static quads), or chair exercises (e.g., ankle pumps, knee extension, arm raise), and will be progressed to performing walking exercises when their physical function improves. Volunteers will check with nursing staff that participants are safe to exercise before each activity session. Participants will receive the mobility sessions twice daily, starting upon recruitment and continuing until the day of discharge from hospital. Training The volunteer training package was developed by a clinician and therapist and will cover topics including patient and personal safety, mobility and exercise training, and response to adverse evets, such as falls. Volunteers will participate in practical sessions to practice the exercises with peers. When ready, volunteers will work with patients, initially under close supervision and when deemed competent by the trainer, they will be encouraged to support mobility sessions independently. A volunteer competency checklist will be completed and signed off by the trainer before volunteers work independently. The training will be delivered by a physiotherapist in each intervention site. Fidelity Checks Throughout the study period, fidelity checks will be conducted by the trainers once every 2 weeks to ensure that the volunteers are delivering high quality and safe exercise. The volunteers will be observed and assessed against a competency and implementation checklist, including personal safety, basic patient safety, pre-intervention tasks (e.g., safe set up of exercise space), and exercise delivery (e.g., showing safe and effective exercise technique). Volunteers will be asked to keep an attendance record during the intervention using session completion logs. Regular monthly volunteer meetings will be scheduled online to discuss experiences and gain feedback from peers and trainers. Based upon fidelity checks and volunteer feedback, extra one-to-one training sessions will be available if necessary. The principle investigator will also visit intervention sites to observe and liaise with volunteers and trainers. Data Collection Data including age, sex, co-morbidities, medications, functional status, and cognition will provide participants' baseline characteristics in both intervention and control sites. Volunteer data including age, occupation, qualifications, volunteering experience, any physiotherapy, sport or therapeutic experience, and employment status will be collected. Data on the study sites including hospital size, size of voluntary service team, the number of hospital volunteers, and information on the therapy services and what usual care looks like will be collected to provide contextual information. The primary outcome measures are feasibility (can it be done?) and acceptability (will volunteers, staff, and patients accept and embrace the programme?) of the intervention. Feasibility will be assessed by: 1. Number of trainers trained and retained in each hospital site (total number and %) 2. Number of volunteers recruited, trained, and retained (total number and %) 3. Recruitment rate (%) of participants in each site 4. Adherence to the intervention (total number and %) Acceptability will be assessed through process evaluation involving: 1. Observation and monitoring of volunteer training 2. Interviews with therapy managers to establish usual care in each site 3. Observation of the interaction between volunteers, patients, and healthcare professionals on the wards, including contextual factors that may potentially influence the delivery and receipt of the intervention. Qualitative interviews will be conducted with service managers, therapy managers, patients, nurses, ward therapists, and volunteers from all study sites, to determine the acceptability of the intervention. Purposive sampling will be conducted to capture a range of experiences and opinions from patients of varying age and mobility levels, staff with varying seniority and gender mix, and volunteers with a range of volunteering experience, age groups, and gender mix. The interviews will explore barriers and facilitators to the implementation of the intervention into routine clinical practice. Fidelity Assessment Fidelity assessment will be conducted across all study sites to ensure that the exercises and prescribed dose are delivered by the volunteers as prescribed. Volunteers will be trained to document each physical activity session in participant exercise diaries, detailing whether all the exercises were carried out as prescribed, or whether some exercises were excluded, and reasons for exclusions. The exercise diaries will be affixed to participants' activity prescription sheet. Further assessments of fidelity of volunteer training and the intervention will be conducted through site visits by the research fellow once every 2 months and to address any issues that arise. Secondary Outcome Measures The secondary outcome measures will include assessment of physical activity levels (StepWatch Activity Monitor; SAM; Modus health, Washington, USA), physical function (Short Physical Performance Battery and grip strength), and quality of life (EuroQol; EQ-5D-5L). Moreover, data on length of hospital stay and hospital readmission will be accessed through electronic patient records. Data collection will be conducted by research nurses, supported by the local principal investigators. Data Analysis Primary Outcome Analyses Participants' baseline characteristics will be described using summary statistics, including mean (standard deviations), medians (interquartile ranges), counts and proportions, as appropriate. Statistical analysis will be conducted using the statistical software SPSS. Summary statistics will be used to describe the feasibility of recruiting, training, and retaining the trainers, the volunteers and study participants. Participants' exercise diaries will be analysed to determine how many physical activity sessions were offered and the number and percentage of completed sessions. Data collected from the interviews will be transcribed verbatim and analysed using thematic analysis (TA). The audio- recordings will be transcribed by an administrative colleague within the research department who is experienced in transcribing qualitative data. TA is a method for identifying, analysing and reporting patterns or themes within data and is widely used in qualitative research. Transcribed text will be read and coded separately and then together by two researchers. The codes will be analysed to generate concepts and ideas to determine the acceptability of the intervention, and to identify facilitators and barriers to the implementation process. The codes act as tags or labels to help catalogue key concepts embedded within the raw data. From the codes, themes will be developed to reflect the views and experiences of the older adults and volunteers regarding the volunteer-led physical activity intervention. Secondary Outcome Analyses Daily step count, Short Physical Performance Battery, grip strength, and quality of life measured on recruitment and discharge, and length of hospital stay will be analysed as continuous variables. The completion rate of each data item will be measured. The distribution of each outcome measure will be assessed for normality and described using parametric or non-parametric statistics accordingly. Hospital readmission in 3 and 6 months will be analysed as a categorical variable. Where there is missing data, the main analyses will be based on available data.

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.

Idiopathic pulmonary fibrosis (IPF) is a progressive and usually fatal lung disease with a poor prognosis. IPF patients frequently have other medical conditions as well, with reflux disease being one of the most common. Previous studies and a review of data already collected suggest that treatments used to reduce reflux disease symptoms, proton pump inhibitors (PPIs), may reduce IPF disease progression and improve survival rates. Current IPF treatment guidelines cautiously advise PPI treatment for IPF patients, however there hasn't been a study which investigates this specifically yet even though doctors and government groups have said one is needed. There are thought to be links between cough, reflux, sleep and IPF. As a result we will be asking a sub-group of patients to complete two 24 hour sessions of cough frequency monitoring as a sub-study. Some of these participants may be asked to wear a wrist-based activity and sleep monitor during these periods also. In addition, we will ask patients to complete two questionnaires on their sleeping habits to further investigate this link. At the end of the trial, we will able to recommend whether or not IPF patients should take PPIs routinely or not. This project is a clinical trial of an investigational medicinal product (drug). The drug is well established and approved for use for another medical condition. The drug will be assessed against placebo (dummy) tablets, with patients allocated to either group by chance. Patients on the drug and dummy tablets will be assessed at the same time. Neither patients nor their doctors or the research team will know which treatment they have been allocated to. We will be running the study at approximately 37 hospitals across the UK. All study visits may take place remotely without the participant needing to attend the hospital. However, face-to-face onsite visits are also permitted if preferred/feasible. All participants will receive central training via video call, with a trained clinical physiologist, following consent on how to complete domiciliary spirometry assessments. Further training will be provided during follow-up if deemed required following a review of the data. Questionnaires will be completed either electronically or by post. Potentially eligible patients will be approached remotely or in clinic after being identified from local patient lists/databases. They will be given/sent the relevant study literature to consider participation in the study and will be followed-up by a member of the local research team after they have had at least 24hours to consider participating. Interested patients will be invited to a virtual or face-to-face screening appointment where they will be counselled on the study and what it entails in order to provide informed consent to participate. The patient will then be asked to complete baseline questionnaires, provide demographic, medical history and concomitant medication, and any other relevant study information, complete spirometry assessments over 5 days at home using a domiciliary spirometer and provide a blood sample for safety in order for the investigator to confirm their eligibility for the trial. Patients may also provide a blood sample for analysis in future research if the visit takes place at the recruiting site. In addition, eligible participants may complete a 24hour period of cough frequency monitoring, and activity and sleep monitoring if applicable, if they have consented to do so. Patients in receipt of PPIs without a clear clinical indication for them at consent, will undergo a two week wash-out period (following agreement from the patient and their GP) to ascertain whether it is safe to stop this treatment and monitor whether their symptoms subside. Patients who remain asymptomatic at the end of this period will proceed to enter the study. For those whose symptoms return, PPI treatment will recommence and they will not enter the study. Once the results of all baseline assessments are known, patients will be randomised. Participants will receive an initial 6 month supply of trial medication and be instructed to take 2 tablets twice daily (approximately 12 hours apart), 30 minutes before meals, for 12 months. Participants will commence weekly domiciliary spirometry assessments, for 12 months, from this point onwards. At 3 months post-randomisation, participants will complete the relevant questionnaires and provide blood samples for safety checks. Domiciliary spirometry assessments remain ongoing. Participants involved in the sub-study will again undergo cough frequency monitoring, and activity and sleep monitoring if applicable, for a final 24 hour period. Patients will be asked to report any changes in their medical history, medication and any events which they have experienced since their last visit. Participants will be contacted again at 6 months post-randomisation where they we will complete questionnaires and provide a safety blood samples. Domiciliary spirometry assessments remain ongoing. Participants will again be asked to report any changes in their medical history, medication and any events which they have experienced since their last visit. Participant adherence to the trial medication will be checked. A final supply of trial medication will be dispensed. At 9 months post-randomisation, local site staff will contact patients to record any changes in their medical history, medication and any events experienced since their last visit. Patients will be required to complete the required questionnaires and provide a blood sample for safety checks. The final study assessments will be at 12 months post-randomisation. Patients will be required to complete all necessary questionnaires, provide a blood sample for safety analysis and a final set of domiciliary spirometry assessments will occur over a 5 day consecutive period. If participants have consented to do so, an additional blood sample will be taken for analysis in future research studies if the visit occurs on site. Patients will be required to report any changes in their medical history, medication and any events they have experienced since their last report to site staff. If participants are suspected of or confirmed to have experienced any of the following they may reduce the dose of their trial treatment, at any point during the study, to 1 tablet, twice daily (approximately 12 hours apart), 30 minutes before meals: infection including pneumonia, Clostridium difficile infection and/or hypomagnesaemia. Participants may also reduce dose if the participant or clinician wishes them to do so. A blood sample for genotype analysis may be taken at any study timepoint which occurs face-to-face, if the participants consents to provide one. Safety blood samples will be taken at the participant's GP surgery where visits take place remotely. Remote follow-up may take place via video or phone call.