CONVINCE
An international, multi-centre, prospective, randomised, controlled study comparing high-dose Haemodiafiltration (HDF) versus conventional high-flux Haemodialysis (HD).

End stage kidney disease (ESKD) ranks among the most severe chronic
non-communicable diseases with an unmet medical need, given the high (between
10% and 20%) and stable annual mortality rates in ESKD patients treated with
dialysis. Kidney replacement therapy is necessary when kidney function is below
roughly 10% of the normal value. Much effort is put into developing strategies
to prevent chronic kidney disease progression. Regenerative medicine is still
in the experimental phase and kidney transplantation is only available for a
small number of patients. Indeed, the everyday reality is the growing number of
dialysis patients. Haemodialysis (HD) treatment is the current standard of care
for the vast majority of patients with ESKD. HD is associated with high risks
of fatal and non-fatal cardiovascular disease, for infections, hospitalisation
and low quality of life. Improvement in the currently available standard is
urgently needed.
Over the past decade, an alternative for haemodialysis became available; called
haemodiafiltration (HDF). HD and HDF are accepted by regulatory authorities.
HDF removes waste products that are accumulated due to kidney failure, more
effectively than standard HD. A individual patient-level data meta-analysis of
the four recent European randomised controlled trials, which comprised 2753
patients with a median follow up of 2.5 years was recently reported. The
results indicate an approximate 22% reduction of mortality risk when convection
volume dosages of > 23 L/session, standardised for Body Surface Area (BSA), was
used. The main beneficial effect was demonstrated by an observed 30% reduction
of cardiovascular mortality and specifically cardiac mortality. Importantly,
the pooled analysis also suggests a 31% reduction in sudden death rate of
borderline significance. A recent large observational study supports the notion
that increased clinical benefit is related to higher dosages. Despite these
recent findings, the scientific community remains critical, largely due to
results that the beneficial effects might be explained by patient selection
(i.e. a healthier patient receives more convection volume). Furthermore, the
mechanism(s) of a possible beneficial effect is/are unproven. This also reduces
the acceptance of the idea of superiority of HDF.

This consortium aims to determine the best possible dialysis treatment by
comparing high-dose HDF versus conventional high-flux HD treatment by carrying
out a prospective randomised controlled clinical trial addressing clinical
endpoints, quality of life and a cost-utility analysis. The CONVINCE study will
deliver an answer on the question which intervention gives the best value for
money. Therefore, it will be considered a *land mark* study, allowing to
publish an *end of discussion* paper.

A multi-centre, controlled, prospective, randomised, open-label trial with
intention-to-treat analyses and a minimum loss to follow-up.

Patients will be randomised between high-dose HDF and high-flux HD treatment.
Both are currently approved methods of dialysis.

As both HD and HDF are current standards of care, the risks are minimal.
At time of randomisation, a physical performance test will be done. During the
trial the patient will be asked to complete questionnaires. No other study
specific tests will be done. The burden for the patient is minimal.