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- Comparative Study of Sevelamer Hydrochloride Versus Calcium Carbonate in Hyperphosphatemic Hemodialysis Patients: An Open-Label, Randomized, Active Controlled, Parallel Study
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題 名 | 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驗 |
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作 者 | 張朝富; 趙玉雯; 賴明育; 莊喬琳; 林堯彬; 唐德成; 陳進陽; 吳采虹; 吳義勇; 陳振文; 楊五常; 林志慶; | 書刊名 | 臺灣腎臟醫學會雜誌 |
卷 期 | 21:1 2007.03[民96.03] |
頁 次 | 頁30-39+80 |
分類號 | 415.816 |
關鍵詞 | 磷能解; 碳酸鈣; 高血磷; 血液透析; Sevelamer; Calcium carbonate; Hyperphosphatemia; Hemodialysis; |
語 文 | 英文(English) |
中文摘要 | 背景:雖然飲食控制及血液透析對於高血磷控制很重要,然而仍然有百分之九十至九十五透析患者需要使用磷結合劑來控制高血磷症。目前市面上磷結合劑大多含有鋁或鈣,而磷能解(sevelamer)是一種不溶解、不被吸收的磷結合劑,可以增加腸道中磷的排出,同時減少如其他磷結合劑可見的全身性副作用。本研究設計是在評估台灣地區高血磷的血液透析患者,使用磷能解與碳酸鈣的效果及安全性比較。方法:首先評估在一個醫學中心的一百七十位血液透析患者。如果停止兩週之磷結合劑後,血磷值仍大於或等於5.5mg/dL,並且簽署同意書而沒有使用磷能解的禁忌才納入研究。最後有四十八位患者納入研究,以一比一的比例同時隨機分配到兩組。在停止使用磷結合劑兩週後,實驗組有二十四位患者使用磷能解,而對照組有二十四位使用碳酸鈣,分別使用八週藥物作為磷結合劑。每兩週依據測量的血磷值(目標值3.5mg/dL至5.5mg/dL)調整研究藥物。試驗結果包括血磷、血鈣、副甲狀腺(iPTH)、血脂肪分析、25(OH)維生素D3及1,25(OH)2維生素D3及其他生化資料。研究結果及生化資料使用SAS軟體分析。P值小於0.05定義為達統計意義。結果:使用磷能解之順從度為百分之88.6,而碳酸鈣為百分之85.6(P=0.5336)。磷能解與碳酸鈣兩組平均血磷值改變分別為-2.86±0.37和-2.67±0.39mg/dL(P=0.7215)。校正後血鈣值在磷能解組下降而碳酸鈣組上升(-0.08±0.16 vs. 0.47±0.17mg/dL, p=0.024)。試驗結束時,兩組之鈣磷乘積(Ca×P)下降程度相當(-28.04±3.94 vs -21.83±4.12mg2/dL2, P=0.282)。副甲狀腺在磷能解組(P=0.001)及碳酸鈣組(P<0.001)兩組都有意義的下降。治療期間副甲狀腺下降中位數在磷能解組及碳酸鈣組兩組分別為-77.6 and -104.6pg/mL。兩組間iPTH下降幅度無統計差異(P=0.6681)。試驗結束時使用磷能解組之膽固醇下降(-50.19±4.24 vs -19.52±4.43mg/dL, P<0.001)及低密度膽固醇下降(-40.83±3.85 vs -14.00±4.02mg/dL, p<0.001)比使用碳酸鈣組幅度大。兩組在高密度膽固醇及三酸甘油脂皆無差異。血中25(OH)維生素D3在兩組改變並無明顯差異,但在第八週時兩組有差異(-1.05±0.71 vs. +1.25±0.77pg/ml, p=0.036)。血中1,25(OH)2維生素D3在兩組內及組間皆無統計差異。血中1,25(OH)2維生素D3在第八週並無明顯差異(P=0.794)。磷能解在整個治療期間患者耐受性良好,磷能解及碳酸鈣兩組副作用發生率相當。結論:在本研究中,磷能解可安全及有效地降低血液透析患者血磷值、鈣磷乘積及副甲狀腺值。其下降程度與使用碳酸鈣相當但是少引起校正血鈣值之上升。另外,磷能解可有效降低低密度膽固醇及總膽固醇值。 |
英文摘要 | 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. |
本系統中英文摘要資訊取自各篇刊載內容。