Trial background

In affected patients, ESKD results in the build-up of small-, middle-, and large-sized toxins that cause cardiovascular damage and impaired immunity. Haemodialysis (HD) is the most common type of dialysis currently provided to treat ESKD in the NHS, and works to remove small- and to a lesser extent middle-sized toxins through diffusion. Haemodiafiltration (HDF) is a newer type of dialysis that is increasingly being adopted in Europe. HDF adds an element of convection to the dialysis process to remove litres of toxin-containing fluid and “substitute” this with sterile fluid. This removes substantially more middle-sized toxins than HD. It is hypothesized that the additional toxin clearance with HDF positively impacts on a broad range of cardiovascular and infection-related outcomes, as has been suggested by post-hoc analyses looking at participants achieving high-volume (21+L of fluid substitution) HDF in several randomised controlled trials (RCTs).

The key aim of the H4RT trial is to determine the relative effectiveness and safety of high-volume HDF compared with high-flux HD on non-cancer mortality and hospital admission with a cardiovascular event or infection in patients with ESKD.

Groups

Adult patients on in-centre maintenance HD for ESKD will be assigned to one of two groups:

1. INTERVENTION: High-volume HDF (aiming for 21+L of substitution fluid per session adjusted to body surface area).
2. COMPARATOR: High-flux HD.

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 will include all-cause mortality, cardiovascular and infection related morbidity and mortality, health-related quality of life, cost effectiveness and environmental impact.