Effect of bixalomer on coronary artery calcification in hemodialysis patients with hyperphosphatemia: a multi-center, randomized controlled trial

Abstract

Abstract Background Calcium carbonate is a first-line therapy for hyperphosphatemia in hemodialysis patients but is associated with progressive coronary and aortic calcification. Sevelamer compounds are alternatives to calcium-containing phosphate binders as they contain lower calcium levels. The sevelamer compound, bixalomer, is a calcium-free insoluble polymer that has been shown to be effective and safe in comparison with calcium carbonate. We therefore compared the effect of bixalomer vs calcium carbonate on coronary artery calcification in hemodialysis patients with hyperphosphatemia. Methods In this open-label, randomized phase IV trial across 23 sites throughout Japan, 85 patients with chronic kidney disease were randomized to bixalomer (n = 44) or calcium carbonate (n = 41) therapy and monitored for 12 months. Bixalomer was administered at a dosage of 1500 mg/day (500 mg three times a day) and calcium carbonate was administered at a dosage of 3000 mg/day (1000 mg three times a day). The primary outcome was the change in coronary artery calcium over time measured using computed tomography. Levels of serum phosphorus, calcium, intact parathyroid hormone, and the occurrence of adverse events were also reported over the course of the study. Results The mean (± standard deviation) changes in coronary artery calcium scores from baseline to 12 months were significantly higher in the calcium carbonate vs bixalomer group (268.6 ± 320.1 vs 126.7 ± 154.8, respectively; between-group difference p = 0.029). At 12 months in the bixalomer group, serum phosphorus and intact parathyroid hormone levels were significantly higher; serum calcium was significantly lower (p < 0.05). The most frequent adverse events were shunt stenosis in the bixalomer group, and shunt stenosis and common cold in the calcium carbonate group. There were no significant between-group differences in adverse drug reaction incidences. Conclusions The safety profile of bixalomer was comparable to that of calcium carbonate. Bixalomer further reduced coronary artery calcification, compared with calcium carbonate, in hemodialysis patients with hyperphosphatemia. Trial registration UMIN/R000015330 Registered 13 February 2014

Keywords

• Bixalomer
• Coronary calcification
• Hemodialysis
• Randomized clinical trial