Design and methods of the REMOVAL-HD study: a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients

R Krishnasamy,C L Nelson,E M Pascoe,M A Roberts,P A Paul-Brent,M J Jardine,C A Hutchison,P F Mount,S Sen,L A Vergara,A Heath,M G Wong,C M Hawley,N D Toussaint,D Darssan,Y J Cho,D W Johnson

doi:10.1186/s12882-018-0883-8

Abstract

BackgroundRemoval of uraemic toxins is inadequate using current dialysis strategies. A new class of dialysis membranes have been developed that allow clearance of larger middle molecules. The REMOVAL-HD study (a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients) will address safety, efficacy and the impact on patient-centred outcomes with the use of a mid cut-off (MCO) dialyser in a chronic haemodialysis (HD) population.MethodsREMOVAL-HD is an open label, prospective, non-randomised, single-arm, multi-centre device study in 85 chronic HD participants. All visits will be conducted during regular HD sessions and participants will undergo a 1 month wash-in period using a standardised high flux dialyser, 6 months of intervention with a MCO dialyser and 1 month of wash-out using a high flux dialyser. The primary endpoint is change in pre-dialysis concentrations of serum albumin, with secondary endpoints including the efficacy of clearance of free light chains and β-2 microglobulin, and patient-centred outcomes including quality of life, symptom burden, functional status, nutritional status, hospitalisation and death.DiscussionMCO dialysers are a novel form of HD membrane. The REMOVAL-HD study is a pivotal study designed to monitor the immediate and medium-term effects following exposure to this dialyser.Trial registrationAustralian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482. Date of registration - 21/06/2016.

Highlights

Removal of uraemic toxins is inadequate using current dialysis strategies
With the advent of high-flux dialysers and haemodiafiltration (HDF), the number of middle-molecules removed by chronic HD programs has continually increased but current HD processes principally only remove molecules with molecular weight cut-offs between
Statistical analysis approach The 95% confidence interval for the mean difference in central serum albumin between 6 months and baseline will be used to assess the change in albumin: a clinically non-meaningful reduction in albumin due to mid cut-off (MCO) dialysis will be inferred if the lower limit of the confidence interval excludes a reduction in serum albumin that is equal to or exceeds 5% of the median serum albumin at baseline

Summary

Introduction

A new class of dialysis membranes have been developed that allow clearance of larger middle molecules. There are still over 20 middle-molecules that are inadequately removed by current dialysis strategies but are potential contributors to chronic inflammation, cardiovascular disease, secondary immunodeficiency and reduced quality of life in dialysis patients [6, 7]. The use of high cut-off membranes was associated with substantial albumin loss and supplementation with human albumin solution was recommended at the end of each dialysis session [6]. These membranes were deemed unsuitable in the setting of chronic HD

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