Title: A randomised controlled trial assessing the effectiveness and cost effectiveness of thrice weekly, extended, in-centre nocturnal haemodialysis versus standard care using a mixed methods approach.
Funder: Department of Health and Social Care

Abstract: Kidney dialysis is a lifesaving treatment for patients with kidney failure with around 24,000 patients receiving regular haemodialysis at a hospital or in a satellite clinic in the UK. Despite the benefits of receiving treatment, people with kidney failure who are on dialysis suffer from lots of intrusive symptoms and ultimately their lives are shortened because of this devastating disease. Most patients have a set dialysis appointment time lasting for 4 hours, 3 times per week, with travel time in addition. This is mainly because it is convenient for the hospital and not the patient. Studies have shown that being treated with the dialysis machine for longer has benefits, but the hard fact is that medical teams struggle to schedule more flexible or extended dialysis schedules due to the volume of patients and finite numbers of machines and staff._x000D_ _x000D_ Nocturnal “in-centre” haemodialysis offers patients something different; the opportunity to have their treatment overnight in a hospital or satellite dialysis clinic while they sleep. Studies suggest that people who have their dialysis overnight may live longer, feel better and may be able to live a life which is closer to normal. Because overnight dialysis (typically 6-8 hours) is a lengthier treatment, it rids the blood of more waste and excess water, acting more like a patients’ normal kidneys which would be working 24/7. As it is more gentle, in particular removing fluid more slowly, it also helps heart function. Importantly, it frees the person up during the day to socialise, work, care for others and generally get more out of life._x000D_ _x000D_ What we know about doing dialysis for longer isn’t perfect though. People who choose to do more dialysis may feel better and live longer for other, completely unrelated reasons. The only way to know for sure is to compare longer treatment times with conventional treatment schedules in a well-designed clinical trial. Previous trials haven’t always measured what matters to people with kidney failure which has made it difficult to assess the impact of a particular treatment on real lives. To make sure these mistakes are not repeated, the current trial has been designed with the help of dialysis patients and medical teams from centres that are already offering overnight dialysis and also from those that don’t._x000D_ _x000D_ This trial asks the question whether six-months of overnight dialysis, performed three times a week in a hospital or satellite centre, improves the quality of life of patients with kidney failure, as compared to those who have shorter dialysis sessions during the day. People who are suitable and consent to take part (and who require dialysis for kidney failure) will be allocated at random, similar to flipping a coin, to either nocturnal dialysis or conventional dialysis. Quality of life will be measured after 6-months of treatment using questionnaires that have been specifically designed for kidney patients. We will also collect information on the extra costs of night-time dialysis, to see whether the new treatment is more cost-effective than conventional dialysis care. Finally, we will evaluate the experiences of patients who are enrolled in the trial to identify barriers to how the treatment would be rolled out across the NHS, if we were to find that it does benefit patients.

Lay abstract: Background: Haemodialysis (HD) can have extensive physiological, psychological and sociological impacts on patients. This is due not just to the physical side effects of HD but also the scheduling of treatment times, which results in patients ‘losing’ three days a week. Patient-reported quality of life is low, with many unable to continue paid employment. In-centre nocturnal HD offers patients the opportunity to dialyse overnight for longer while asleep. Despite growing evidence in support, it remains underutilised due to both equipoise in the renal community and uncertainty from commissioners about the cost benefit of implementation._x000D_ _x000D_ Aim: To measure the effect of a 6-month programme of extended hours, in-centre nocturnal haemodialysis (INHD) on quality of life._x000D_ _x000D_ Design: A pragmatic, two-arm, multi-centre, randomised controlled trial with a health economic analysis. An in-trial pilot with an on-going process evaluation is embedded in this study_x000D_ _x000D_ Randomisation: Patients will be allocated 1:1.33 to account for an additional 25% non-adherence rate in the intervention group using minimisation. Groups will be stratified by site and age._x000D_ _x000D_ Target population: All prevalent adult patients receiving HD (or haemodiafiltration) in an out-patient hospital or satellite HD unit. Patients will be excluded if they: lack capacity to consent; have a life expectancy of less than, or are expecting a living kidney donor transplant within, 6 months; for whom allocation to standard hours care of 4-hours thrice weekly during the day would be clinically unacceptable._x000D_ _x000D_ Health technology assessed: Patients allocated to the intervention group will receive 6-8 hours of HD delivered overnight, three times per week for 6-months. Controls will receive standard care (3.5-5 hours three times per week during the day). All other dialysis care will remain the same. _x000D_ _x000D_ Objective: The overall aim of this trial is to test the clinical and cost effectiveness of thrice weekly, extended hours nocturnal dialysis compared to standard dialysis care thrice weekly during the day. _x000D_ _x000D_ Primary outcome measure: Patient reported quality of life at 6-months measured using the composite score from the Kidney Disease Quality of Life tool (KDQoL). Secondary outcome measures: Additional quality of life questionnaires, safety and process measures._x000D_ _x000D_ Sample size: The trial is powered to detect a 5-point difference in the KDQoL between groups at 6-months adjusted for baseline, the minimal clinically important difference for that instrument. To achieve 90% power and a type I error rate of 5%, 256 participants are required. Assuming an overall attrition rate of 15%, and 25% non-adherence with INHD in the intervention group, the targeted number of randomisations is 350._x000D_ _x000D_ Analysis: The analysis will be by intention to treat. Point estimates and 95% confidence intervals from two-sided tests will be calculated for all main outcome measures. A Statistical Analysis Plan will be drawn up prior to any analysis and reviewed by the independent Data Safety Monitoring Committee._x000D_ _x000D_ Timelines: Months 1-12 set up; Months 7-24 in-trial pilot and parallel process evaluation, recruitment commencing in 4 units with existing INHD programmes at month 12 and 4 additional units by month 24; Month 36 all 18 units open; Month 48 complete follow-up; Month 54 database lock; Month 60 complete dissemination of results.

Research activity codes: 6.3 MEDICAL DEVICES;7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: RENAL AND UROGENITAL