Evaluating the effects of sevelamer carbonate on cardiovascular structure and function in chronic renal impairment in Birmingham: the CRIB-PHOS randomised controlled trial

Abstract

Background: Serum phosphate is an independent predictor of cardiovascular morbidity and mortality in patients with chronic kidney disease and the general population. There is accumulating evidence that phosphate promotes arterial stiffening through structural vascular alterations such as medial calcification, which are already apparent in the early stages of chronic kidney disease.

Aim: To determine the effects of phosphate binding with sevelamer carbonate on left ventricular mass and function together with arterial stiffness in patients with stage 3 chronic kidney disease.

Methods/design: A single-centre, prospective, randomised, double-blind, placebo-controlled trial of 120 subjects with stage 3 chronic kidney disease recruited from University Hospitals Birmingham NHS Foundation Trust. Baseline investigations include transthoracic echocardiography and cardiac magnetic resonance imaging to assess ventricular mass, volumes and function, applanation tonometry to determine pulse wave velocity and pulse wave analysis as surrogate measures of arterial stiffness and dual energy x-ray absorptiometry scanning to determine bone density. During an open-label run in phase, subjects will receive 1600 mg sevelamer carbonate with meals for four weeks. They will then be randomised to either continue sevelamer carbonate or receive an identical placebo (60 subjects per arm) for the remaining 36 weeks. Four-weekly monitoring of serum electrolytes and bone biochemistry will be performed. All baseline investigations will be repeated at the end of the treatment period. The primary endpoint of the study is a reduction in left ventricular mass after 40 weeks of treatment. Secondary endpoints are: i) change in aortic compliance; ii) change in arterial stiffness; iii) change in arterial elastance; iv) change in left ventricular systolic and diastolic elastance; v) change in left ventricular function; and vi) change in bone density.

Trial registration: This trial is registered at ClinicalTrials.gov: NCT00806481 and Current Controlled Trials: ISRCTN35254279.

Figure 1

Study timeline. 120 subjects will undergo baseline investigations before entering a 4 week open-label run-in phase in which all subjects will receive 1600 mg of sevelamer carbonate with meals. Participants will then be randomised to continue treatment with sevelamer carbonate 1600 mg with meals or identical placebo for the remaining 36 weeks. Safety monitoring will be performed every four weeks. Investigations will be repeated at week 40 after which subjects will have completed participation in the study.