Title: BioImpedance Spectroscopy to maintain Renal Output: The BISTRO Trial
Funder: Department of Health and Social Care

Abstract: DESIGN: Pragmatic, multicentre, open-label prospective randomised controlled trial comparing current best practice in setting the post-dialytic target weight with the same guided by serial BI measurements. BI readings will be taken in both study groups but concealed from the clinical team in the controls. SETTING: Adult outpatient haemodialysis units (main and satellite) and renal ward during hospital admission. TARGET POPULATION: Adults >18 years commencing out-patient maintenance haemodialysis, planned/unplanned, with or without permanent access, including incremental initiation INCLUSIONS - Residual kidney function: >500 ml for the short interdialytic gap and/or a measured mean urea and creatinine clearance > 3ml/min/1.73m2 EXCLUSIONS -Unable/unwilling to give informed consent -Unable to comply with trial procedures. -Likely survival prognosis or planned modality transfer <3 months. -Subjects with amputations (this will depend on the level of lower limb loss), pregnancy PRIMARY OUTCOME: time to anuria, <100 ml/day or 200 ml in the short interdialytic period confirmed by a further collection after 2 weeks to exclude temporary illness. SECONDARY OUTCOMES - Slope of decline of residual renal solute clearance. - Patient-centred outcomes: Dialysis-related symptoms; Intra-dialytic hypotension; Post-dialysis recovery time; Falls; Inter-dialytic weight gain; Physical function (Duke ASI); Patient Activation Measure; and QOL as required for the economic evaluation -Significant Events: hospitalisations, interventions, deaths. -Body composition/nutrition (BI derived) -Health economics outcomes SAMPLE SIZE Assuming a cumulative incidence of anuria of 30% in the control group and 20% in the treatment group, accounting for 11% competing risks (death, transplantation) – given exponential decline, proportional hazards, 90% power and 5% two-tailed significance - 185 events are required. Allowing for 5% loss to follow-up this requires 516 patients to be randomised 1:1. For the secondary outcome of rate of decline in renal clearance, at the same significance level this sample size would provide at least 90% power to detect a difference in rate of 0.05 ml/min/1.73m2/month, assuming linear change, assessments at 0, 1, 2, 3, 5, 7, 9, 11 and 13 months, and a (conservative)autocorrelation of 0.30. ANALYSIS Time to anuria will be analysed using competing risks survival analysis to estimate the relative risk (as expressed by the sub-hazard ratio) of the outcome (anuria) in patients where BI is used compared to control patients, accounting for the competing risks (death, transplantation). The analysis will control for known covariates affecting residual function, e.g. comorbidity, antihypertensive and diuretic use. Difference in rate of decline in renal clearance will be analysed using a random slopes linear mixed model. Corresponding appropriate analyses will be used for the other secondary outcomes. Pre-specified subgroup analyses will be limited to comorbid conditions that affect management of fluid status e.g. heart failure. For the economic evaluation base-case analysis will adopt the perspective of the NHS and personal social services with additional analyses undertaken from a wider societal perspective. Results will be presented as cost per additional QALY and plotted as cost-effectiveness acceptability curves.

Lay abstract: Aims of the research: To test whether taking regular measurements with a bioimpedance device, which gives information about body composition, improves outcomes for people who have newly started haemodialysis treatment for their kidney failure. In particular we want to see if this helps maintain their remaining kidney function as this is associated with improved survival, fewer symptoms of kidney failure, fewer side effects of the dialysis treatment and a better quality of life. We also want to see if sharing the bioimpedance information with patients leads to greater involvement and participation in their treatment. Background to the research: Most patients who develop kidney failure choose unit-based haemodialysis treatment. One of the main functions of dialysis is to control the amount of fluid in the body; too much fluid can lead to harm such as a persistently raised blood pressure that damages the heart and increases the risk of stroke, and may cause fluid to collect in the lungs leading to breathing difficulties which if allowed to get out of control increases the risk of death. Too little fluid, often as a result of trying to avoid these problems, causes dehydration, cramps and low blood pressure on dialysis and more rapid or complete loss of any remaining kidney function along with its associated benefits. Bioimpedance is a simple, bedside measurement giving information about body composition, in particular how much excess fluid is present. Clinicians can use this to guide how much fluid should be removed by dialysis in conjunction with the normal clinical assessment of the amount of fluid in the body but it is not known if this results in better decisions and outcomes for patients. The bioimpedance information can be shared with patients to help them understand the objectives of their treatment, potentially improving confidence in how their dialysis care is managed. Design and methods used: We will invite people starting haemodialysis treatment as an outpatient who still have some remaining kidney function to participate in a clinical trial that compares current best practice with the same but additionally guided by regular bioimpedance measurements. We will randomly assign 516 patients from 33 dialysis units across the UK. This is a sufficient number for us to determine whether the additional use of bioimpedance reduces the risk of complete loss of kidney function in the first year of treatment from 3 in 10 patients to 2 in 10 patients. We will also compare between treatments how quickly kidney function is declining, the side effects of treatment, symptoms of kidney failure, blood pressure and heart function, patient–reported measures including confidence in managing their health, as well as robust information to enable a cost benefit analysis of the intervention. Patient and public involvement: We have worked closely with the NIHRs Devices for Dignity (D4D) Healthcare Technology Co-operative Renal Theme to develop this study. D4D has a strong PPI focus on technology adoption with links to INVOLVE and a patient network group. Members of this network will be invited to become members of an advisory group advising on study design, patient recruitment and dissemination. We will publicise the findings of this study through conferences, peer reviewed publications, the D4D Media Centre, National Kidney Federation (KidneyLife) and British Kidney Patients Association, including articles written by patients for patients. Website: https://www.keele.ac.uk/bistro/ Twitter: @Keele_CTU

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RENAL AND UROGENITAL