帕立骨化醇与骨化三醇治疗3-4期慢性肾脏病继发性甲状旁腺功能亢进的随机多中心试验。
A randomized multicenter trial of paricalcitol versus calcitriol for secondary hyperparathyroidism in stages 3-4 CKD.
作者信息
Coyne Daniel W, Goldberg Seth, Faber Mark, Ghossein Cybele, Sprague Stuart M
机构信息
Renal Division, School of Medicine, Washington University, St. Louis, Missouri;
Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, Michigan;
出版信息
Clin J Am Soc Nephrol. 2014 Sep 5;9(9):1620-6. doi: 10.2215/CJN.10661013. Epub 2014 Jun 26.
BACKGROUND AND OBJECTIVES
Calcitriol is used to treat secondary hyperparathyroidism in patients with CKD. Paricalcitol is less calcemic and phosphatemic in preclinical studies and in some trials in dialysis patients, but head-to-head comparisons in nondialysis patients are lacking. A large meta-analysis of trials concluded that these agents did not consistently reduce parathyroid hormone (PTH) and increased the risk of hypercalcemia and hyperphosphatemia. Therefore, the objective of this multicenter trial was to compare the rate of hypercalcemia between calcitriol and paricalcitol, while suppressing PTH 40%-60%.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with stages 3-4 CKD (n=110) with a PTH level >120 pg/ml were recruited and randomized to 0.25 μg/d of calcitriol or 1 μg/d of paricalcitol between April 2009 and July 2011. Subsequent dose adjustments were by protocol to achieve 40%-60% PTH suppression below baseline. The primary endpoint was the rate of confirmed hypercalcemia of >10.5 mg/dl between groups.
RESULTS
Forty-five patients in each group completed the 24 weeks of treatment. Both agents suppressed PTH effectively (-52% with paricalcitol and -46% with calcitriol; P=0.17), although the paricalcitol group reached a 40% reduction in PTH sooner at a median 8 weeks (interquartile range [IQR], 4, 12) versus 12 weeks (IQR, 8, 18; P=0.02) and had a lower pill burden of 240 (IQR, 180, 298) versus 292 (IQR, 231, 405; P=0.01). Confirmed hypercalcemia was very low in both groups (three with paricalcitol and one with calcitriol) and was not significantly different (P=0.36). Both groups had small increases in calcium and phosphorus levels (0.3-0.4 mg/dl in each electrolyte) and significant decreases in alkaline phosphatase, a marker of high bone turnover, with no significant differences between groups.
CONCLUSIONS
These results show that both calcitriol and paricalcitol achieved sustained PTH and alkaline phosphatase suppression in stages 3-4 CKD, with small effects on serum calcium and phosphorus and a low incidence of hypercalcemia.
背景与目的
骨化三醇用于治疗慢性肾脏病（CKD）患者的继发性甲状旁腺功能亢进。在临床前研究以及一些针对透析患者的试验中，帕立骨化醇的血钙和血磷升高作用较弱，但在非透析患者中缺乏直接对比研究。一项大型试验的荟萃分析得出结论，这些药物并不能持续降低甲状旁腺激素（PTH）水平，反而增加了高钙血症和高磷血症的风险。因此，这项多中心试验的目的是比较骨化三醇和帕立骨化醇在抑制PTH 40%-60%时高钙血症的发生率。
设计、地点、参与者及测量指标：招募110例3-4期CKD患者，其PTH水平>120 pg/ml，于2009年4月至2011年7月随机分为骨化三醇0.25 μg/d组或帕立骨化醇1 μg/d组。随后根据方案调整剂量，以使PTH水平较基线降低40%-60%。主要终点是两组间确诊的血钙水平>10.5 mg/dl的发生率。
结果
每组45例患者完成了24周的治疗。两种药物均能有效抑制PTH（帕立骨化醇组降低52%，骨化三醇组降低46%；P=0.17），尽管帕立骨化醇组在第8周（四分位间距[IQR]，4，12）时PTH水平较基线降低40%，早于骨化三醇组的第12周（IQR，8，18；P=0.02），且每日服药量较低，分别为240（IQR，180，298）和292（IQR，231，405；P=0.01）。两组确诊的高钙血症发生率均很低（帕立骨化醇组3例，骨化三醇组1例），差异无统计学意义（P=
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