The High-volume Haemodiafiltration vs High-flux Haemodialysis Registry Trial (H4RT)

Design: A non-blinded randomised controlled trial comparing the clinical and cost-effectiveness of two dialysis methods – high-volume HDF and high-flux HD. Randomisation: 1:1, stratified by site, age and residual renal function. The primary analysis will be intent to treat using proportional hazards regression adjusting for variables used to stratify the randomisation. Setting: Secondary care renal units. Target population: Adult patients on in-centre, maintenance HD for ESKD Exclusion criteria: Lack of capacity to consent; Clinician predicted life expectancy less than 3 months; On maintenance HD less than 4 weeks; Living kidney donor transplant or home dialysis scheduled within 3 months; Treatment with HDF for more than 3 months prior to recruitment to the trial or prior intolerance of HDF; Not suitable for high-volume HDF for other clinical reasons. Health technology assessed: Intervention= High-volume HDF (aiming for 21+L of substitution fluid per session adjusted to body surface area (1)) Comparator= High-flux HD aiming for a small solute clearance comparable to the high-volume HDF Difference between current and planned care In HD and HDF toxins are removed by diffusion, but in HDF there is also (i) convection to remove 21+L of toxin-containing fluid and (ii) substitution/ replacement of that volume with 21+L of sterile fluid. For the patient, the treatment appears very similar with the same frequency and duration. Measurement of costs and outcomes The primary outcome will be a composite of non-cancer mortality or hospital admission with a cardiovascular event or infection within 3 years. Secondary outcomes with include all-cause mortality, cardiovascular and infection related morbidity and mortality, health-related quality of life (QoL), cost-effectiveness and environmental impact. Basleine data will be collected by research personnel, but all follow up data will be collected continuously by the Registry from renal electronic health records, linkage to health care databases and patient questionnaires. Sample size The trial is powered to be able to detect a clinically meaningful 25% reduction in the composite primary end-point (HR 0.75) based on 65% of participants experiencing this end-point over a median of 3 years follow up. To optimise recruitment and avoid excluding eligible patients because they are already participating /want to participate in other trials, an additional adjustment has been made that assumes up to half of patients in both groups will take part in another trial. Adjustment has also been made anticipating cross-over between arms (15% from HD to HDF & 5% from HDF to HD). The number of events required to detect this difference with 90% power and a two-sided 5% significance level is 801, which requires 1348 participants in total. To allow for 10% loss to follow-up, we require 1527 participants and will recruit 1550. (See Section 6.7 in the detailed project description for details.) Project timetables and recruitment rate Following set-up in months 1-6, recruitment will begin in 20 sites over 18 months (months 7-24), i.e. 78 patients per site. Participation is estimated at 30% of eligible patients initially, increasing to 40% after 4 months with Quintet Recruitment Intervention (2). Participants will be followed through the UK Renal Registry to month 56 (minimum 2 years 8 months, median 3 years) with analysis and write up in months 57-60.