Can we IMPROVE cardiovascular outcomes through phosphate lowering in CKD? Rationale and protocol for the IMpact of Phosphate Reduction On Vascular End-points in Chronic Kidney Disease (IMPROVE-CKD) study. Issue 2 (21st February 2019)

• Record Type: Journal Article
• Authors: Lioufas, Nicole; Toussaint, Nigel D; Pedagogos, Eugenia; Elder, Grahame; Badve, Sunil V; Pascoe, Elaine; Valks, Andrea; Hawley, Carmel
• Other Names: author non-byline.; Toussaint Nigel D author non-byline.; Pedagogos Eugenia author non-byline.; Lioufas Nicole author non-byline.; Hawley Carmel M author non-byline.; Elder Grahame J author non-byline.; Pascoe Elaine M author non-byline.; Valks Andrea author non-byline.; Badve Sunil V author non-byline.; Block Geoffrey A author non-byline.; Boudville Neil C author non-byline.; Campbell Katrina author non-byline.; Cameron James D author non-byline.; Chen Sylvia Sm author non-byline.; Faull Randall J author non-byline.; Holt Stephen G author non-byline.; Hooi Lai S author non-byline.; Jackson Dana author non-byline.; Jardine Meg J author non-byline.; Johnson David W author non-byline.; Kerr Peter G author non-byline.; Lau Kenneth K author non-byline.; Morrish Alicia author non-byline.; Perkovic Vlado author non-byline.; Polkinghorne Kevan R author non-byline.; Pollock Carol A author non-byline.; Reidlinger Donna author non-byline.; Robison Laura author non-byline.; Smith Edward R author non-byline.; Walker Robert J author non-byline.; Moon wang Angela Yee author non-byline.;
• Is Part Of: BMJ open. Volume 9:Issue 2(2019)
• Publication Date: 2019-02-21
• Subjects: phosphate -- mineral metabolism -- randomized controlled trial -- ckd-mbd -- pulse wave velocity -- vascular calcification; Medicine -- Research -- Periodicals; 610.72
• DOI: 10.1136/bmjopen-2018-024382
• Languages: English
• ISSNs: 2044-6055

Abstract

Abstract : Introduction: Patients with chronic kidney disease (CKD) are at heightened cardiovascular risk, which has been associated with abnormalities of bone and mineral metabolism. A deeper understanding of these abnormalities should facilitate improved treatment strategies and patient-level outcomes, but at present there are few large, randomised controlled clinical trials to guide management. Positive associations between serum phosphate and fibroblast growth factor 23 (FGF-23) and cardiovascular morbidity and mortality in both the general and CKD populations have resulted in clinical guidelines suggesting that serum phosphate be targeted towards the normal range, although few randomised and placebo-controlled studies have addressed clinical outcomes using interventions to improve phosphate control. Early preventive measures to reduce the development and progression of vascular calcification, left ventricular hypertrophy and arterial stiffness are crucial in patients with CKD. Methods and analysis: We outline the rationale and protocol for an international, multicentre, randomised parallel-group trial assessing the impact of the non-calcium-based phosphate binder, lanthanum carbonate, compared with placebo on surrogate markers of cardiovascular disease in a predialysis CKD population—the IM pact of P hosphate R eduction O n V ascular E nd-points (IMPROVE)-CKD study. The primary objective of the IMPROVE-CKD study is to determine if the use of lanthanum carbonate reduces the burden of cardiovascular disease in patients with CKD stages 3b and 4 when compared with placebo. The primary end-point of the study is change in arterial compliance measured by pulse wave velocity over a 96-week period. Secondary outcomes include change in aortic calcification and biochemical parameters of serum phosphate, parathyroid hormone and FGF-23 levels. Ethics and dissemination: Ethical approval for the IMPROVE-CKD trial was obtained by each local Institutional Ethics Committee for all 17 participating sites in Australia, New Zealand and Malaysia prior to study commencement. Results of this clinical trial will be published in peer-reviewed journals and presented at conferences. Trial registration number: ACTRN12610000650099.