Chronic Kidney Diseases Clinical Trials in United Kingdom

The purpose of this single-arm interventional study is to evaluate the long-term safety, efficacy, and durability of the Symplicity Spyral system in subjects treated with renal denervation. Additionally, long-term follow-up data will also be collected from eligible subjects previously treated in the SPYRAL PIVOTAL-SPYRAL HTN-OFF MED and SPYRAL HTN-ON MED studies. Read Less

The purpose of this study is to assess the safety and efficacy (including durability) of up to 2 REACT injections given 3 months (+30 days) apart and delivered percutaneously into biopsied and non-biopsied contralateral kidneys in participants with T2DM and CKD. Read Less

The goal of this observational study is to evaluate safety and performance of GORE® ACUSEAL Vascular Graft for the treatment of CKD in patients with ESRD in hemodialysis. The main questions it aims to answer are: * Safety: Freedom from device-related infection adverse events at 24 months from device implant * Performance: Secondary patency at 24 months from device implant. Participants, after informed consent is obtained, will be implanted with GORE® ACUSEAL Vascular Graft and followed for 24 months in standard of care, to evaluate safety and performance of the device. Read Less

Rationale: * People with long term kidney disease who are on haemodialysis (a procedure for removing waste products from the blood) commonly develop a condition that makes their skin very itchy. * Difelikefalin is a medicine that can treat the itching related to long term kidney disease. * Clinical studies have shown difelikefalin to reduce itching in adults on haemodialysis, while being safe and tolerable. * The current study is being done in adolescents aged 12 to 17 years on haemodialysis who have moderate to severe itching related to long term kidney disease to assess if difelikefalin is safe in this age group. The aims of the study are: Main aim: To assess the safety of difelikefalin in adolescents who are on haemodialysis and have itching related to long term kidney disease Secondary aim: To measure the amount of difelikefalin that enters the blood in adolescents who are on haemodialysis and have itching related to long term kidney disease Study Design At least 18 adolescents, aged 12 to 17 years, who are on haemodialysis and have itching related to long term kidney disease will take part in this study. All study participants will receive difelikefalin 3 (or up to 4) times weekly for up to 12 weeks. The study duration for a participant is up to 17 to 18 weeks; during this period, participants will visit the clinic 3 times weekly (during their haemodialysis visits). Read Less

Health inequality and genetic disparity are a significant issue in the United Kingdom (UK). This study focuses on diseases that are associated with significant morbidity and mortality in the UK, and specifically examines the extent and basis of treatment failure in different patient populations. The vast majority of drug registration clinical trials have under-representation of ethnic minority populations. In addition, the wider Caucasian populations have reasonably different clinical characteristics to the population that participated in the drug licencing clinical trials. A consequence of this is that drugs are licensed for use in real-world general patient populations where the clinical trial results are simply not statistically significant to specifically demonstrate efficacy or safety in populations that were either absent or under-represented in the drug registration clinical trials. When these facts are considered alongside data that supports significant under-reporting of adverse events in the real-world setting within the UK (and globally, e.g the USA and Europe), it highlights that pharmacovigilance systems are unable to capture drug effectiveness and safety data in a manner that can reasonably assure appropriate prescribing in the wider patient populations. This large real-world research study aims to identify whether commonly prescribed drugs are effective in treating illnesses that cause significant poor health and death in the different patient populations that represent the UK. The goal of this study is to generate large quantitative data-sets that may inform clinical practice to reduce the existing health inequality and genetic disparity in the UK. Read Less

In health, blood pressure (BP) falls at night by \>10% compared with day-time values. This natural dipping pattern is important as without it there is an increased risk of cardiovascular disease (CVD). Recent evidence suggests that chronotherapy (taking anti-hypertensive medication at bedtime instead of in the morning) may enhance nocturnal BP dipping and reduce the risk of CVD events. There is therefore an urgent need to characterise diurnal BP patterns in patients who may be at risk of reduced nocturnal dipping in order to maximise protective therapy in all those who would benefit. Similarly, it has previously been demonstrated that increased arterial stiffness is associated with increased CVD risk, however little is known about whether loss of diurnal variations in arterial stiffness confer addition risk. Kidney disease is independently associated with increased CVD events, but the exact makeup of this risk is not clear. Within this heterogenous cohort several very distinct groups exist including those with acute kidney injury (AKI), chronic kidney disease (CKD), inflammatory conditions like small vessel vasculitis (SVV), and those who have either donated or received a kidney transplant. Diurnal BP and arterial stiffness patterns within these patient groups are not well characterised. The investigators will recruit patients at increased risk of CVD from the Royal Infirmary of Edinburgh Renal and Vasculitis Clinics. Participants will undergo 24-hour ambulatory BP and arterial stiffness measurement in conjunction with day- and night-time blood and urine sampling on two separate occasions. This study aims to characterise diurnal patterns of BP and arterial stiffness in patients at increased risk of CVD and compare findings with healthy controls. In doing so, the investigators aim to allow more targeted CVD risk reduction strategies and improve long-term patient outcomes. Read Less

This is a feasibility study to assess new, more practical ways of measuring renal reserve. Read Less

Research goals: To explore the views and baseline knowledge of children and young people (CYP) with CKD and their caregivers to develop effective phosphate educational materials (PEM), adapted for age, and acknowledging different learning styles Read Less

Haemodialysis is a renal replacement therapy that can be introduced to patients with end-stage renal disease (ESRD) to help them maintain a good healthy life. The patient's blood is pumped through a dialysis machine to remove excess fluid, salt and waste, then it is pumped back into the patient's circulation system. In order to carry out haemodialysis, vascular access (VA) is required to connect the patient to the dialysis machine. Patients have only three options of vascular access: arteriovenous fistula (AVF), an anastomosis between a native vein and an artery; arteriovenous graft (AVG), a connection between a synthetic tube and native blood vessels; and (3) central line, a cuffed catheter placed in a large neck vein. Arteriovenous fistulas are the preferred method for VA because of their longevity and causing the least number of complications. Although there are a number of factors that may increase the probability of AVF failure rate such as age and gender of the patient, poor native vessel structure, medications and the level of surgical experience, 30-40% of new AVFs fail to mature for unknown reasons. For an AVF to become functionally mature postoperative, remodelling and dilation of the native artery and vein are essential to accommodate significantly increased blood flow. However, pre-existing diseases in patients with ESRD such as arterial stiffness and endothelial dysfunction may impair AVF and preclude dialysis. It has been asserted that the lack of AVF success is attributable to insufficient arterial dilation because of poor arterial wall elasticity. The study aims to investigate the role of arterial stiffness and endothelial dysfunction in predicting AVF outcome using novel non-invasive ultrasound applications: 2D shear wave elastography and 2D strain speckle tracking will be employed to assess arterial stiffness, while an intraoperative flow-mediated dilation (FMD) technique will be used to evaluate endothelial dysfunction. Read Less

Background Chronic kidney disease (CKD) is a progressive condition characterised by a gradual reduction in kidney function and structure over time. CKD is a risk factor for other morbidity, where it not only increases the likelihood of all-cause and cardiovascular mortality, but also can have a detrimental impact on quality of life. Whilst several systematic reviews have demonstrated the benefits of interventions delivered by pharmacists, there is significant variability in terms of the outcomes reported and an inconsistency with the measures used (e.g., medication adherence is often assessed using different outcome measures). The large heterogeneity of outcomes reported and the measures used in randomised controlled trials investigating the impact interventions involving pharmacists have on CKD patients makes it difficult to interpret findings and make comparisons between interventions have. This ultimately affects the quality of research and limits the ability to synthesize evidence, particularly in meta-analyses. Issues around inconsistent outcome reporting could be addressed with the development and application of agreed standardised sets of outcomes. Indeed, the significant range of outcomes in the CKD pharmacy literature led the authors in Raiisi et al., to state that further research is required to establish a core outcome set (COS) in CKD, in relation to pharmacy practice. COS are a collection of outcomes that are standardised and agreed upon, in which as a minimum, they should be measured and reported in all trials for a particular clinical topic. They are of importance as input is provided from a variety of stakeholders such as patients, researchers, family members, carers, and healthcare professionals, in which relevant outcomes are more likely to be identified, as well as helping reduce reporting bias and heterogeneity in the research literature. Currently no pharmacy-specific COS exists for interventions conducted in CKD. Aims The overall objective is to develop a COS for clinical trials evaluating the efficacy or effectiveness of pharmacist-led interventions (i.e., interventions provided to patients are either pharmacist-led or involve their input) in people with CKD. The aim of Phase 1 is to conduct an online survey to explore outcomes of importance to stakeholders. The outcomes identified in Phase 1 will lead into a subsequent Delphi process to develop a COS (Phase 2). Methods Phase 1 The investigators aim to use an online survey to collect data from participants. The questions in this survey can be found in the attached documentation. It is estimated that this survey will take 10 minutes to complete. The first part of the survey asks questions about the participant including what stakeholder group best describes them. The second part asks them about what outcomes are important in pharmacy research and in the management of kidney disease. Phase 2 The outcomes generated in this survey will be supplemented by outcomes identified in an ongoing systematic review performed by the research group. The investigators will take this long-list of outcomes and aim to reach a consensus on a COS using a 2-round Delphi process. The Delphi process is a structured process used for forming a consensus, where stakeholder groups provide their opinions in an iterative approach for answering questions over several rounds. This will also take place using surveys online and the investigators will submit an ethical amendment for each round with the questions and outcomes we will be seeking consensus on. In each Delphi round, participants will be asked to rate the importance of outcomes for inclusion or exclusion. Between each round, excluded outcomes will be removed. Included outcomes (those reaching consensus, defined as a minimum of 75% of participants who scored outcomes as agree or strongly agree or disagree or strongly disagree) will go into the COS. Following the Delphi survey, the investigators will conduct a consensus day. A sample of participants will be invited to discuss the findings and reach a consensus on the final COS. Read Less

This study aims to find out whether people with chronic kidney disease \[CKD\] should take low dose aspirin to reduce the risk of first heart attack or stroke (cardiovascular disease \[CVD\]). CKD is common and is associated with an increased risk of CVD. CVD is caused by small blood clots and aspirin thins the blood to reduce the risk of such clots developing but it also increases the risk of bleeding. Aspirin is recommended to prevent further CVD in people who have already had a first CVD event (so called secondary prevention). Here the investigators want to study the use of aspirin as primary prevention in people with CKD who have not had a CVD to prevent the first event, to assess whether the potential benefits exceed the risks. Eligible patients will be recruited from their United Kingdom (UK) general practices and allocated by chance to be prescribed once daily low dose aspirin or usual care only. Follow-up will be for several years both electronically (for general practice, hospital and mortality data) and by annual questionnaires to ascertain CVD and bleeding events. Read Less

Background: CKD in patients with heart failure (HF) is common and associated with poor prognosis. Despite evidence of benefit with Renin-Angiotensin-Aldosterone-System inhibitor (RAASi) agents, they are avoided due to fear of hyperkalaemia. New potassium binders, e.g. Sodium Zirconium Cyclosilicate (SZC), reduce incidence of hyperkalaemia in CKD-HF patients and hence may help RAASi maximisation, which has not been investigated in an RCT. Purpose: The proposed study will randomise HFrEF patients with stable CKD 3-5 and serum potassium 5-5.0 mmol/L, to receive SZC or placebo while RAASi therapy is maximised. The aim of the study is to examine if SZC is superior to placebo in achieving maximal doses of ACEi/ARB, e.g. Ramipril 10 mg, Candesartan 32 mg; and mineralocorticoid receptor antagonist, e.g. Epleronone 50 mg or Spironolactone 50 mg, avoiding hyperkalaemia. Methods: Eligible patients with eGFR\<60 mL/min/1.73m2, heart failure (EF\<40%) on none/submaximal dose of RAASi will be randomised to receive 10g TDS of investigational medicinal product (IMP), either SZC or placebo, for 48 hours and in 10 or 5g OD guided by laboratory serum potassium (K+). Every two weeks the RAASi dose will be increased and IMP adjusted according to a strict protocol and guided by laboratory potassium and creatinine. The primary endpoint of the study is achievement of maximal dose of RAASi in randomised patients avoiding hyperkalaemia, i.e. K+≤5.6 mmol/L. Patients will be allowed to continue with RAASi maximisation to K+\<6.0mmol/L. Patients will be tested at baseline and follow-up visits for hyperkalaemia, AKI, symptomatic hypotension and QT prolongation on ECG. Results: The study results will show if SZC is superior to placebo for RAASi maximisation in CKD-HF patients while maintaining safe levels of serum potassium without any adverse impact on quality of life. The study will demonstrate if SZC allows higher RAASi dose and more dose escalations than placebo. It will also examine the impact of RAASi escalation on creatinine, proteinuria, and cardiac blood biomarkers. Conclusion: If positive, the results of this study will demonstrate that SZC enables RAASi up titration in CKD-HF patients, which potentially can help achieve optimal treatment and improve quality of life of the patient. Read Less