All Clinical Trials in United Kingdom

Acute Respiratory Distress Syndrome (ARDS) is a severe type of lung injury that affects 10% of patients admitted to Intensive Care Units worldwide, with an unacceptably high mortality of up to 48% in those with the most severe form of the condition. It is a complex and poorly understood syndrome that results in progressive failure of the lungs. Crucially, the inflamed lungs allow fluid to leak from the circulation into the airspace, so that patients' lungs fill with fluid - "drowning from the inside". As this condition progresses, the patient typically requires increasing amounts of oxygen and eventually, support from a ventilator. To date, there are no effective treatments for ARDS that can limit, stop or repair this process. This research study is aiming to look at a naturally occurring substance produced by blood vessels, C-type natriuretic peptide (CNP). The investigators have evidence suggesting that CNP plays a role in maintaining the barrier provided by blood vessels that stops fluid leaking out into tissues. This is based on various studies done on CNP by the investigators research group that have established its widespread role in maintaining cells that line blood vessels and play a vital role in lungs' barrier function: the endothelium. CNP is broken down in part by an enzyme called Neutral endopeptidase and therefore, drugs that inhibit this enzyme would result in increased CNP concentration and activity. If CNP does in fact strengthen the lungs' endothelial barrier, then this class of drug may benefit patients with ARDS. The aim of this experimental medicine study is to assess the effect of using the licensed NEP inhibitor Racecadotril, in a well-established, safe model of inflammation-induced skin blisters in healthy human volunteers to determine primarily whether the fluid accumulation i.e. leak, in these blisters is reduced by treatment with this drug. Read Less

The goal of this clinical trial is to test a new type of pacemaker in heart failure patients following a heart bypass operation. The new pacemaker restores respiratory sinus arrhythmia which is a natural pattern where the heart rate increases when the participants breathe in and slows down when participants breathe out. The main questions the trial aims to answer are: * Is the new type of pacemaker safe? * Does the new type of pacemaker improve how patients' hearts work (also known as cardiac output)? Participants will have a range of tests before their operation and during their recovery in hospital while participants have the new type of pacemaker in place, and will be monitored very closely. Participants will also receive a phone call 1 month after their surgery. Researchers will compare the new type of heart pacing against standard treatment to see if it is as safe, and if it is any better for patients. Read Less

Physiological cardiovascular stress test plays a crucial role in the assessment of patients with suspected heart disease. There are several methods of cardiac physiological stress tests and each of them offer varied insight into cardiac physiological adaptation: passive leg raise, intra-venous fluid challenge, pharmacological stressors and physical exercise stress test. Echocardiography, which is the mainstay for the non-invasive rest/stress assessment of the left ventricular (LV) haemodynamics has several limitations. Novel methods of CMR imaging allow to map intra-cardiac flow in three-dimension using novel flow acquisitions. These novel flow acquisitions are called four-dimensional flow CMR, where the fourth dimension is time. Additionally, traditional cine CMR imaging for functional assessment can now be done without breath-holds using advanced acceleration methods, allowing them to be used during exercise. A comprehensive understanding of functional-flow coupling at rest, during increased pre-load (fluid challenge) to the heart or during exercise, is lacking in the literature. There is an important need to validate these novel CMR methods for developing mechanistic insight into physiological cardiac adaptation to increased pre-load or to exercise in health and how it alters in heart disease. Read Less

1. FULL TITLE OF THE PROJECT Should we use post-operative antibiotics following surgery for patients with mandible fractures? The MANTRA trial (MANdibular TRauma and Antibiotic use) 2. SUMMARY OF RESEARCH (ABSTRACT) Research Question: Are post-operative antibiotics required following surgery for patients with mandible fractures? Background: Mandible fractures are the commonest facial fractures needing surgery and account for a significant percentage of the acute workload in Oral \& Maxillofacial Surgery (OMFS) units. The UK records over 6000 new cases per year. Patients having surgery for mandible fractures have a theoretical risk of developing surgical site infection, due to the proximity of the fracture lines to the oral cavity microbes and the presence of foreign body (titanium fixation miniplates). For this reason, clinicians often prescribe antibiotics after surgery, to reduce the risk of infection. Previous systematic reviews and a multicentre cohort study performed by this team, revealed significant clinical variation in post-operative antibiotic prescription amongst UK OMFS clinicians and the presence of clinical equipoise. Antibiotic overuse can lead to antibiotic resistance and other antibiotic-related side effects; judicious antibiotic use and stewardship is of paramount importance. Aim: To determine whether post-operative antibiotics are required at all, following surgery for mandible fractures, and, if so, what is the most clinically- and cost-effective regimen Objectives: Primary Objective To conduct a Randomized Controlled Trial (MANTRA) in order to establish the non-inferiority (or not) of not giving post-operative antibiotics versus 2 other post-operative antibiotic regimens. An internal pilot phase will optimise recruitment and retention. Secondary Objectives * Measure the cost-effectiveness of the proposed antibiotic pathways * Assess patient and clinician acceptability to change clinical practice * Process evaluation to inform dissemination and implementation Methods: The investigators designed and propose the MANTRA RCT to compare 3 post-operative antibiotic approaches to prevent Surgical Site Infections (SSIs) following surgery for mandible fractures. The MANTRA trial is a large open label, multicentre study in NHS OMFS units. The 3 study arms represent the most common clinical pathways in the UK based on previous work; the control group is the approach prescribed by most UK OMFS clinicians. All patients will receive 1 dose of IV antibiotics (co-amoxiclav 1.2g, if no penicillin allergy, which is the most commonly used prophylactic antibiotic currently) on induction of anaesthesia, prior to their surgery. The participants will be randomised to the following (1:1:1): Group A: No further antibiotics Group B: 2 further postoperative IV doses of co-amoxiclav 1.2g Group C: 2 further postoperative IV doses (as above), followed by a 5-day course of oral co-amoxiclav 625mg every 8 hours if no penicillin allergy (Control). Trial processes will be optimised by an internal pilot phase ensuring we recruit, randomise, and retain participants with clear progression criteria. We will also conduct cost-effectiveness analyses and process evaluation for dissemination and implementation Timeline: Start of grant: 1st July 2023 Start of RCT / pilot: 1st January 2024 End of pilot: 30th June 2024 End of recruitment: 31st December 2026 End of follow-up: 30th June 2027 Completion: 31st December 2027 Impact and dissemination: * Practice changing outputs that standardise the use of antibiotics in mandible fractures in the NHS and provide a framework for other surgical prophylaxis research * A bespoke clinical dissemination plan via an engagement and training legacy * Cost-effectiveness data to inform policy making * A research legacy and change of culture in the specialty of OMFS Read Less

This is a first-in-human, open-label, non-randomized, three-part phase 1 trial of INBRX-109, which is a recombinant humanized tetravalent antibody targeting the human death receptor 5 (DR5). Read Less

STUDY OVERVIEW Brain injury can result in a loss of consciousness or awareness, to varying degrees. Some injuries are mild and cause relatively minor changes in consciousness. However, in severe cases a person can be left in a state where they are "awake" but unaware, which is called unresponsive wakefulness syndrome (UWS, previously known as a vegetative state). Up to 43% of patients with a UWS diagnosis, regain some conscious awareness, and are then reclassified as minimally conscious after further assessment by clinical experts. Many of those in the minimally conscious state (MCS) and all with unresponsive wakefulness syndrome (UWS) are incapable of providing any, or consistent, overt motor responses and therefore, in some cases, existing measures of consciousness are not able to provide an accurate assessment. Furthermore, patients with locked-in syndrome (LIS), which is not a disorder of consciousness as patients are wholly aware, also, struggle to produce overt motor responses due to paralysis and anarthria, leading to long delays in accurate diagnoses using current measures to determine levels of consciousness and awareness. There is evidence that LIS patients, and a subset of patients with prolonged disorders of consciousness (DoC), can imagine movement (such as imagining lifting a heavy weight with their right arm) when given instructions presented either auditorily or visually - and the pattern of brain activity that they produce when imagining these movements, can be recorded using a method known as electroencephalography (or EEG). With these findings, the investigators have gathered evidence that EEG-based bedside detection of conscious awareness is possible using Brain- Computer Interface (BCI) technology - whereby a computer programme translates information from the users EEG-recorded patterns of activity, to computer commands that allow the user to interact via a user interface. The BCI system for the current study employs three possible imagined movement combinations for a two-class movement classification; left- vs right-arm, right-arm vs feet, and left-arm vs feet. Participants are trained, using real-time feedback on their performance, to use one of these combinations of imagined movement to respond to 'yes' or 'no' answer questions in the Q\&A sessions, by imagining one movement for 'yes' and the other for 'no'. A single combination of movements is chosen for each participant at the outset, and this participant-specific combination is used throughout their sessions. The study comprises three phases. The assessment Phase I (sessions 1-2) is to determine if the patient can imagine movements and produce detectable modulation in sensorimotor rhythms and thus is responding to instructions. Phase II (sessions 3-6) involves motor-imagery (MI) -BCI training with neurofeedback to facilitate learning of brain activity modulation; Phase III (sessions 7-10) assesses patients' MI-BCI response to closed questions, categorized to assess biographical, numerical, logical, and situational awareness. The present study augments the evidence of the efficacy for EEG-based BCI technology as an objective movement-independent diagnostic tool for the assessment of, and distinction between, PDoC and LIS patients. Read Less

Malignant pleural effusion remains a debilitating complication of end stage cancer, which can be greatly improved by the introduction of the indwelling tunneled pleural catheter (IPC). However, there is no standard of care regarding drainage and limited data on the utility of different drainage techniques. In addition, many patients develop discomfort and chest pain during drainage. The investigators propose to evaluate gravity drainage and suction drainage on quality of life measures and outcomes. Read Less

The main aim of the Tessa Jowell BRAIN MATRIX - Platform Study is to more precisely determine the exact type of tumour patients have by developing the essential infrastructure to provide rapid and accurate molecular diagnosis. A large network of clinical hubs across the United Kingdom, with expertise in managing patients with brain tumours, will be developed. Once established this infrastructure will facilitate the rapid introduction of clinical trials testing targeted therapies tailored to the genetic changes of an individual's tumour. Read Less

Heart Failure occurs when the heart's ability to pump blood is reduced. Heart failure can lead to symptoms of breathlessness, fatigue and ankle swelling, and result in health complications including damage to other organs (e.g. kidneys), reduced function and quality of life. Although the symptoms of heart failure are similar for men and women, there are sex differences. Lifestyle behaviours such as physical activity are important modifiable risk factor for heart failure. Women continue to be underrepresented in heart failure studies and treatment guidelines are male-derived due to these disparities in recruitment. The purpose of the present study is to evaluate the physical activity levels, sedentary behaviour, sleep and quality of life and understand the barriers and facilitators to these lifestyle behaviours in women newly diagnosed with heart failure. Read Less

Using magnetic resonance (MR) imaging or spectroscopy as part of clinical research typically involves developing new MR protocols. Although some of this work is done by scanning artificial 'phantoms', volunteer studies are normally needed to configure and validate new protocols appropriately. Developing new MR protocols and techniques is also useful in its own right. The volunteer scanning described in this application will provide data to support this type of methodological research into new scanning and image processing techniques: improving the speed, quality, and range of measurements possible with the scanner. With proper safety and screening procedures, MR has no known side-effects, and has been performed on millions of human subjects worldwide without ill effect. There are well-established contraindications for MRI, and screening procedures are already in place in the MR unit at UCLH to exclude such subjects and ensure the safety of subjects. With these, and the MR scanner's built in safety mechanisms, residual risk is low. Many other trusts with active MR research have previously made similar applications to this related to volunteer MR scanning for pilot work and methodological research Although scans may obtained as part of several research projects, in each case it is only the scanning technique (the programmed sequence of data acquisition and processing steps) which will vary, along with the body region to be imaged. The volunteer experience will be very similar, and all ethical issues, including the information sheet and consent form, will be identical. These scans are for methodological research on the MR techniques themselves, and will be never form part of the volunteer's own healthcare. Separate ethical permission is sought for any study which does not match the above criteria. Read Less

Multi-site, open-label, first-in-human study with 2 parts (dose escalation and dose expansion) in subjects with selected advanced solid tumours Read Less

The goal of this observational study is to improve the early detection of lung cancer in adults who have smoked less than 100 tobacco cigarettes ("never-smokers") in the United Kingdom. The main questions it aims to answer are: * To describe characteristics such as demographics, co-morbidities and environmental exposures * To describe participant pathways including presentation mode and symptoms to understand if earlier diagnosis would be possible * To describe participant outcomes such as cancer stage, treatment and mortality * To quantitatively or qualitatively measure modifiable and non-modifiable factors that may be associated with LCINS including environmental measures, blood tests and genomic data. Participants will currently have no change to their usual care. Read Less