Wetmore James B, Gurevich Konstantin, Sprague Stuart, Da Roza Gerald, Buerkert John, Reiner Maureen, Goodman William, Cooper Kerry
Division of Nephrology, Hennepin County Medical Center, Minneapolis, Minnesota;
Fresenius Medical Care, St. Petersburg, Russia;
Clin J Am Soc Nephrol. 2015 Jun 5;10(6):1031-40. doi: 10.2215/CJN.07050714. Epub 2015 Apr 22.
Direct comparison of cinacalcet and vitamin D analogs as monotherapies to lower parathyroid hormone (PTH) levels has not been undertaken.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective, multicenter, phase 4, randomized, open-label study that enrolled participants from 2010 to 2012. Adult participants (n=312) on hemodialysis with PTH >450 pg/ml were randomized 1:1 to 12 months of treatment with either cinacalcet (n=155) or vitamin D analogs (n=157) to evaluate the mean percentage change in plasma PTH level (primary end point) and the proportion of participants achieving plasma PTH <300 pg/ml or a ≥30% decrease in PTH (secondary end points). A preplanned analysis to determine whether there were important region-by-treatment interactions was also undertaken.
Baseline mean PTH was 846 pg/ml (n=155) for cinacalcet and 816 pg/ml (n=157) for vitamin D analog therapy. The mean (95% confidence interval) percentage change from baseline in PTH was -12.1% (-20.0% to -4.1%) in the cinacalcet arm and -7.0% (-14.9% to 0.8%) in the vitamin D analog arm, a difference of -5.0% (-15.4% to 5.4%) (P=0.35). Similarly, there was no difference in achievement of secondary efficacy end points between arms (19.4% and 15.3% of participants with PTH≤300 pg/ml and 42.6% and 33.8% of participants had a PTH reduction >30% in the cinacalcet and vitamin D analog arms, respectively). A prespecified analysis revealed a large treatment-by-region interaction, with nominally greater response to cinacalcet compared with vitamin D analogs in non-United States participants (US versus non-US participants, P<0.001). Hypocalcemia was more common in the cinacalcet arm, whereas hypercalcemia and hyperphosphatemia occurred more often in the vitamin D analog arm.
Participants had similar modest reductions in PTH with either cinacalcet or vitamin D analog monotherapy over 52 weeks of treatment, but effects varied by region. Treatments differed with regard to effect on calcium and phosphorus levels.
尚未对西那卡塞和维生素D类似物作为单药治疗降低甲状旁腺激素（PTH）水平进行直接比较。
设计、地点、参与者及测量指标：这是一项前瞻性、多中心、4期、随机、开放标签研究，于2010年至2012年招募参与者。PTH>450 pg/ml的成年血液透析参与者（n = 312）按1:1随机分为两组，分别接受12个月的西那卡塞治疗（n = 155）或维生素D类似物治疗（n = 157），以评估血浆PTH水平的平均百分比变化（主要终点）以及血浆PTH<300 pg/ml或PTH降低≥30%的参与者比例（次要终点）。还进行了一项预先计划的分析，以确定是否存在重要的治疗区域交互作用。
西那卡塞组基线平均PTH为846 pg/ml（n = 155），维生素D类似物治疗组为816 pg/ml（n = 157）。西那卡塞组PTH较基线的平均（95%置信区间）百分比变化为-12.1%（-20.0%至-4.1%），维生素D类似物组为-7.0%（-14.9%至0.8%），差异为-5.0%（-15.4%至5.4%）（P = 0.35）。同样，两组间次要疗效终点的达成情况无差异（西那卡塞组和维生素D类似物组分别有19.4%和15.3%的参与者PTH≤300 pg/ml，42.6%和33.8%的参与者PTH降低>30%）。一项预先指定的分析显示存在较大的治疗区域交互作用，在非美国参与者中，西那卡塞的反应名义上大于维生素D类似物（美国与非美国参与者比较，P<0.001）。低钙血症在西那卡塞组更常见，而高钙血症和高磷血症在维生素D类似物组更常发生。
在52周的治疗中，西那卡塞或维生素D类似物单药治疗的参与者PTH均有相似的适度降低，但效果因地区而异。两种治疗对钙和磷水平的影响不同。
