Comparative Study of Sevelamer Hydrochloride versus Calcium Carbonate in Hyperphosphatemic Hemodialysis Patients: An Open-Label, Randomized, Active Controlled, Parallel Study

在高血磷血液透析患者使用磷能解(sevelamer hydrochloride)與碳酸鈣之比較實驗：一個開放標籤、隨機、主動控制之平行對照試險

張朝富(Chao-Fu Chang) ； 趙玉雯(Yu-Wen Chao) ； 賴明育(Ming-Yu Lai) ； 莊喬琳(Chiao-Lin Chuang) ； 林堯彬(Yao-Ping Lin) ； 唐德成(Der-Cherng Tarng) ； 陳進陽(Jinn-Yang Chen) ； 吳采虹(Tsai-Hung Wu) ； 吳義勇(Yee-Yung Ng) ； 陳振文(Tzen-Wen Chen) ； 楊五常(Wu-Chan)

《Acta Nephrologica》 21卷1期 (2007/03) Pp. 30-39

摘要

Background: Although dietary phosphate restriction and regular dialysis play important roles in the management of hyperphosphatemia, approximately 90-95% of dialysis patients have to utilize phosphate binders to control their hyperphosphatemia. Current phosphate binders on the market contain either aluminum or calcium. Sevelamer hydrochloride, an insoluble, non-absorbable phosphate-binding polymer, was synthesized to enhance phosphate excretion while minimizing the systemic effects observed with other phosphate binders. The present study is designed to evaluate the efficacy and the safety profiles of sevelamer versus calcium carbonate in Taiwanese hemodialysis patients with hyperphosphatemia.
Methods: One hundred and seventy maintenance hemodialysis patients in a medical center were evaluated. Patients were included if they were hyperphosphatemic (≥5.5mg/dL) during the 2 weeks washout period and signed the informed consent without a contraindication. Forty-eight patients were included and randomized into two groups by 1:1 ratio. After the withdrawal of all phosphate binders for a washout period of 2 weeks, one group (n=24) took sevelamer as the phosphate binder and the other group (n=24) used calcium carbonate for a treatment period of 8 weeks. The dosages of study drugs were adjusted every 2 weeks according to serum phosphorus levels (target 3.5mg/dL to 5.5mg/dL). The study outcomes included serum phosphorus, serum calcium, intact parathyroid hormone (iPTH), lipid profile, 25-hydroxyvitamin D3[25(OH)D3], 1, 25-dihydroxyvitamin D3[1, 25(OH)2D3] and other clinical biochemical data. The clinical parameters and biochemical data were analyzed by using SAS software. A result with a p value less than 0.05 is statistically significant.
Results: The overall compliance was 88.6% with sevelamer hydrochloride and 85.6% with calcium carbonate treatment (p=0.5336). Mean changes from baseline in serum phosphorus were -2.86±0.37 and -2.67±0.39mg/dL, in sevelamer and calcium carbonate groups, respectively (p 0.7215). The adjusted serum calcium level decreased in the sevelamer group but elevated in the calcium carbonate group (-0.08±0.16 vs. 0.47±0.17mg/dL, p=0.024). By the end of this study, both treatment groups lowered the calcium × phosphorus (Ca × P) product with the same extent (-28.04±3.94 vs. -21.83±4.12 mg2/dL2, p=0.282). Serum iPTH levels significantly decreased in both sevelamer (p=0.001) and calcium carbonate groups (p＜0.001). The median change in serum iPTH during the treatment period was -77.6 and -104.6pg/mL in sevelamer hydrochloride and calcium carbonate groups, respectively. The difference between the groups for the change in iPTH was not statistically significant (p=0.6681). Upon completion of this study, those subjects receiving sevelamer reduced their serum total cholesterol (-50.19±4.24 vs. -19.52±4.43mg/dL, p＜.0001) and LDL-cholesterol (-40.83±3.85 vs. -14.00±4.02mg/dL, p＜0.001) much more than those receiving calcium. The HDL-cholesterol and triglyceride did not change in both treatment groups. Plasma 25(OH)D3 level didn't change significantly in those groups; however, the difference between the two treatment groups was statistically significant at week 8 (-1.05±0.71 vs. +1.25±0.77pg/ml, p=0.036). Plasma 1, 25(OH)2D3 level didn't change significantly within or between the two treatment groups. The mean change in plasma 1, 25(OH)2D3 was not significant at week 8 (p=0.794). Sevelamer was well tolerated by subjects in the overall treatment period. The incidence of adverse events was similar between sevelamer and calcium carbonate groups.
Conclusions: In this study, sevelamer safely and effectively reduced serum phosphorus, Ca × P product and iPTH in hemodialysis patients. The reduction in sevelamer treatment was similar to calcium carbonate treatment but with less increased adjusted calcium. Additionally, sevelamer treatment significantly reduced LDL cholesterol and total cholesterol.

關鍵字

磷能解sevelamer ； 碳酸鈣 ； 高血磷 ； 血液透析

並列摘要

Background: Although dietary phosphate restriction and regular dialysis play important roles in the management of hyperphosphatemia, approximately 90-95% of dialysis patients have to utilize phosphate binders to control their hyperphosphatemia. Current phosphate binders on the market contain either aluminum or calcium. Sevelamer hydrochloride, an insoluble, non-absorbable phosphate-binding polymer, was synthesized to enhance phosphate excretion while minimizing the systemic effects observed with other phosphate binders. The present study is designed to evaluate the efficacy and the safety profiles of sevelamer versus calcium carbonate in Taiwanese hemodialysis patients with hyperphosphatemia.
Methods: One hundred and seventy maintenance hemodialysis patients in a medical center were evaluated. Patients were included if they were hyperphosphatemic (≥5.5mg/dL) during the 2 weeks washout period and signed the informed consent without a contraindication. Forty-eight patients were included and randomized into two groups by 1:1 ratio. After the withdrawal of all phosphate binders for a washout period of 2 weeks, one group (n=24) took sevelamer as the phosphate binder and the other group (n=24) used calcium carbonate for a treatment period of 8 weeks. The dosages of study drugs were adjusted every 2 weeks according to serum phosphorus levels (target 3.5mg/dL to 5.5mg/dL). The study outcomes included serum phosphorus, serum calcium, intact parathyroid hormone (iPTH), lipid profile, 25-hydroxyvitamin D3[25(OH)D3], 1, 25-dihydroxyvitamin D3[1, 25(OH)2D3] and other clinical biochemical data. The clinical parameters and biochemical data were analyzed by using SAS software. A result with a p value less than 0.05 is statistically significant.
Results: The overall compliance was 88.6% with sevelamer hydrochloride and 85.6% with calcium carbonate treatment (p=0.5336). Mean changes from baseline in serum phosphorus were -2.86±0.37 and -2.67±0.39mg/dL, in sevelamer and calcium carbonate groups, respectively (p 0.7215). The adjusted serum calcium level decreased in the sevelamer group but elevated in the calcium carbonate group (-0.08±0.16 vs. 0.47±0.17mg/dL, p=0.024). By the end of this study, both treatment groups lowered the calcium × phosphorus (Ca × P) product with the same extent (-28.04±3.94 vs. -21.83±4.12 mg2/dL2, p=0.282). Serum iPTH levels significantly decreased in both sevelamer (p=0.001) and calcium carbonate groups (p＜0.001). The median change in serum iPTH during the treatment period was -77.6 and -104.6pg/mL in sevelamer hydrochloride and calcium carbonate groups, respectively. The difference between the groups for the change in iPTH was not statistically significant (p=0.6681). Upon completion of this study, those subjects receiving sevelamer reduced their serum total cholesterol (-50.19±4.24 vs. -19.52±4.43mg/dL, p＜.0001) and LDL-cholesterol (-40.83±3.85 vs. -14.00±4.02mg/dL, p＜0.001) much more than those receiving calcium. The HDL-cholesterol and triglyceride did not change in both treatment groups. Plasma 25(OH)D3 level didn't change significantly in those groups; however, the difference between the two treatment groups was statistically significant at week 8 (-1.05±0.71 vs. +1.25±0.77pg/ml, p=0.036). Plasma 1, 25(OH)2D3 level didn't change significantly within or between the two treatment groups. The mean change in plasma 1, 25(OH)2D3 was not significant at week 8 (p=0.794). Sevelamer was well tolerated by subjects in the overall treatment period. The incidence of adverse events was similar between sevelamer and calcium carbonate groups.
Conclusions: In this study, sevelamer safely and effectively reduced serum phosphorus, Ca × P product and iPTH in hemodialysis patients. The reduction in sevelamer treatment was similar to calcium carbonate treatment but with less increased adjusted calcium. Additionally, sevelamer treatment significantly reduced LDL cholesterol and total cholesterol.

並列關鍵字

sevelamer ； calcium carbonate ； hyperphosphatemia ； hemodialysis