Original Investigation
Dialysis
Sevelamer Versus Calcium Carbonate in Incident Hemodialysis Patients: Results of an Open-Label 24-Month Randomized Clinical Trial

https://doi.org/10.1053/j.ajkd.2013.03.023Get rights and content

Background

Whether the use of sevelamer rather than a calcium-containing phosphate binder improves cardiovascular (CV) survival in patients receiving dialysis remains to be elucidated.

Study Design

Open-label randomized controlled trial with parallel groups.

Settings & Participants

466 incident hemodialysis patients recruited from 18 centers in Italy.

Intervention

Study participants were randomly assigned in a 1:1 fashion to receive either sevelamer or a calcium-containing phosphate binder (although not required by the protocol, all patients in this group received calcium carbonate) for 24 months.

Outcomes

All individuals were followed up until completion of 36 months of follow-up or censoring. CV death due to cardiac arrhythmias was regarded as the primary end point.

Measurements

Blind event adjudication.

Results

At baseline, patients allocated to sevelamer had higher serum phosphorus (mean, 5.6 ± 1.7 [SD] vs 4.8 ± 1.4 mg/dL) and C-reactive protein levels (mean, 8.8 ± 13.4 vs 5.9 ± 6.8 mg/dL) and lower coronary artery calcification scores (median, 19 [IQR, 0-30] vs 30 [IQR, 7-180]). At study completion, serum phosphate levels were lower in the sevelamer arm (median dosages, 4,800 and 2,000 mg/d for sevelamer and calcium carbonate, respectively). After a mean follow-up of 28 ± 10 months, 128 deaths were recorded (29 and 88 due to cardiac arrhythmias and all-cause CV death). Sevelamer-treated patients experienced lower CV mortality due to cardiac arrhythmias compared with patients treated with calcium carbonate (HR, 0.06; 95% CI, 0.01-0.25; P < 0.001). Similar results were noted for all-cause CV mortality and all-cause mortality, but not for non-CV mortality. Adjustments for potential confounders did not affect results.

Limitations

Open-label design, higher baseline coronary artery calcification burden in calcium carbonate–treated patients, different mineral metabolism control in sevelamer-treated patients, overall lower than expected mortality.

Conclusions

These results show that sevelamer compared to a calcium-containing phosphate binder improves survival in a cohort of incident hemodialysis patients. However, the better outcomes in the sevelamer group may be due to better phosphate control rather than reduction in calcium load.

Section snippets

Study Participants

A detailed description of the INDEPENDENT (Reduce Cardiovascular Calcifications to Reduce QT Interval in Dialysis) Study has been published elsewhere.21 Study participants were randomly assigned in a 1:1 fashion to receive either sevelamer hydrochloride or a calcium-containing phosphate binder (although not required by the protocol, all patients in this group received calcium carbonate; Fig 1). Adult (aged >18 years) patients with CKD stage 5 new to hemodialysis (requiring dialysis <120 days)

Results

A total of 466 patients were randomly assigned to treatment with either sevelamer (n = 232) or a calcium-containing phosphate binder (n = 234). Of these, 33 (14.2%) in the sevelamer arm and 36 (15.3%) in the calcium carbonate arm exited the study for various reasons prior to study completion, for a drop-out rate <5% per year (Fig 1). Enrollment and drop-out rates were well balanced across all sites (Table S1). Mean age of the study cohort was 65 ± 14 years. Men and women were represented

Discussion

In this study, a large cohort of incident hemodialysis patients was randomly assigned to receive either sevelamer or calcium carbonate for treatment of hyperphosphatemia. The primary objective of the study was to test the impact of phosphate-binder assignment on CV mortality due to cardiac arrhythmias and secondarily on all-cause CV mortality and all-cause mortality. Previous randomized clinical trials have shown that sevelamer may significantly attenuate the progression of CV calcification in

Acknowledgements

The INDEPENDENT Study Investigators are as follows: Filippo Aucella (S. Giovanni Rotondo), Pasquale Guastaferro, Angela Di Gianni (S. Angelo Dè Lombardi), Luigi Chiuchiulo (Avellino, Dyalysis), Roberto Rubino (Ariano Irpino), Lucia Di Micco (Napoli), Vincenzo Tedesco (Montella), Mario Migliorati (S. Giorgio A Cremano), Walter De Simone, Bruno Zito (Avellino), Ernesto D'avanzo, Francesco Saverio Iannaccone (Solofra: Radiologia), Maria Luisa Sirico (Caserta), Patrizia Veniero, Maria Capuano,

References (30)

  • W.N. Suki

    Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients: results of a randomized clinical trial

    J Ren Nutr

    (2008)
  • G.A. Block et al.

    Mineral metabolism, mortality, and morbidity in maintenance hemodialysis

    J Am Soc Nephrol

    (2004)
  • K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease

    Am J Kidney Dis

    (2003)
  • KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD)

    Kidney Int Suppl

    (2009)
  • T. Isakova et al.

    Phosphorus binders and survival on hemodialysis

    J Am Soc Nephrol

    (2009)
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    Originally published online May 20, 2013.

    Corrected online July 30, 2013. See Item S1 in “Supplementary Material” online for an explanation of the corrections. The errors have been corrected in the print, PDF, and HTML versions of this article.

    Trial registration: www.ClinicalTrials.gov; study number: NCT00710788.

    Deceased.

    A list of the INDEPENDENT Study Investigators appears in the Acknowledgements.

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