title: A Study to Inform the Design of a National Multicentre Randomised Controlled Trial to Evaluate If Reducing Serum Phosphate to Normal Levels Improves Clinical Outcomes including Mortality, Cardiovascular Events, Bone Pain, or Fracture in Patients on Dialysis.
abstract: Background. Retrospective, observational studies link high phosphate with mortality in dialysis patients. This generates research hypotheses but does not establish "cause-and-effect." A large randomised controlled trial (RCT) of about 3000 patients randomised 50 : 50 to lower or higher phosphate ranges is required to answer the key question: does reducing phosphate levels improve clinical outcomes? Whether such a trial is technically possible is unknown; therefore, a study is necessary to inform the design and conduct of a future, definitive trial. Methodology. Dual centre prospective parallel group study: 100 dialysis patients randomized to lower (phosphate target 0.8 to 1.4 mmol/L) or higher range group (1.8 to 2.4 mmol/L). Non-calcium-containing phosphate binders and questionnaires will be used to achieve target phosphate.
  
  
  METHODS
  percentage successfully titrated to required range and percentage maintained in these groups over the maintenance period. Secondary endpoints: consent rate, drop-out rates, and cardiovascular events. Discussion. This study will inform design of a large definitive trial of the effect of phosphate on mortality and cardiovascular events in dialysis patients. If phosphate lowering improves outcomes, we would be reassured of the validity of this clinical practice. If, on the other hand, there is no improvement, a reassessment of resource allocation to therapies proven to improve outcomes will result. Trial Registration Number. This trial is registered with ISRCTN registration number ISRCTN24741445.
authors.affiliation: Institute of Cardio-Vascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PL, UK ; Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
authors.forename: Ramya
authors.initials: R
authors.lastname: Bhargava
authors.affiliation: Salford Royal Hospitals NHS Foundation Trust, Salford M6 8HD, UK ; Institute of Population Studies, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PL, UK.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kalra
authors.affiliation: Institute of Cardio-Vascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PL, UK ; Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Brenchley
authors.affiliation: Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Hurst
authors.affiliation: Institute of Cardio-Vascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PL, UK ; Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
authors.forename: Alastair
authors.initials: A
authors.lastname: Hutchison