Reichel H, Braun J
Nephrologisches Zentrum, Schwenningen.
Dtsch Med Wochenschr. 2011 Jan;136(4):123-8. doi: 10.1055/s-0030-1247876. Epub 2010 Dec 21.
The calcimimetic cinacalcet (Mimpara) was approved in the European Union in 2004 for treatment of secondary hyperparathyroidism (sHPT). This observational trial was conducted to investigate efficacy of cinacalcet and practices of sHPT treatment under routine clinical conditions.
913 patients on maintenance hemodialysis were recruited from 136 German kidney centers. 662 patients who fulfilled the entry criteria of moderate to severe sHPT (intact parathyroid hormone, iPTH: 300 - 800 pg/mL or 32 - 85 pmol/l) were included in the trial. Primary objective was to investigate efficacy of cinacalcet in patients treated for at least 160 days (efficacy collective, N = 555). The primary endpoint was defined as the percentage of patients with a iPTH within 150 - 300 pg/ml and a calcium-phosphate product (CaxP) ≤ 4.44 mmol (2)/l (2) (55 mg (2)/dl (2)) after 6 months of treatment. Further objectives were the course of calcium (Ca) and phosphate (P) as well as the use of phosphate binders and vitamin D in treatment of bone metabolism disorders.
According to the predefined entry criteria none of the patients reached the combined target criterion for iPTH and CaxP at baseline. The mean initial iPTH and CaxP were 530.0 ± 134.3 pg/mL and 4.82 mmol (2)/L (2) (mean ± SD) respectively. In spite of the unfavorable prognostic factors 25 % of the recruited patients met the combined target at the end of the trial. The mean reduction per patient for iPTH was 203.6 pg/mL [95 % confidence interval (CI) 183.3 - 224.0] and 0.69 mmol (2)/L (2) [95 %-CI 0.57 - 0.79] for CaxP. Ca and P were reduced by 5.3 % [95 %-CI 4.3 - 6.3] and 5.5 % [95 %-CI 3.4 - 7.7], respectively. The mean daily dose of cinacalcet at trial end was 44.9 ± 25.0 mg (mean ± SD). At baseline, 90 % of patients who were analyzed for efficacy (n = 500/555) were treated with phosphate binders, 57 % were treated with a calcium-based phosphate binder (n = 317/555). The use of active Vitamin D (all active Vitamin D compounds) was recorded for 59 % of the patients (n = 328/555). No relevant changes of these treatments were observed in the course of the trial. Tolerability of cinacalcet was good, 94 adverse drug reactions were recorded in 57 of the 913 enrolled patients (6 %).
One out of four patients reached the combined target of iPTH and CaxP with relatively low dose cinacalcet after 6 months of treatment. iPTH, Ca and P were reduced. The results confirm the high efficacy of cinacalcet in treatment of sHPT and underline the role of cinacalcet in the control of Ca and P.
拟钙剂西那卡塞（Mimpara）于2004年在欧盟获批用于治疗继发性甲状旁腺功能亢进（sHPT）。本观察性试验旨在研究西那卡塞在常规临床条件下治疗sHPT的疗效及治疗方法。
从136个德国肾脏中心招募了913例维持性血液透析患者。662例符合中度至重度sHPT纳入标准（全段甲状旁腺激素，iPTH：300 - 800 pg/mL或32 - 85 pmol/l）的患者被纳入试验。主要目的是研究西那卡塞在治疗至少160天的患者中的疗效（有效组，N = 555）。主要终点定义为治疗6个月后iPTH在150 - 300 pg/ml且钙磷乘积（CaxP）≤4.44 mmol²/L²（55 mg²/dl²）的患者百分比。其他目的包括钙（Ca）和磷（P）的变化过程以及在治疗骨代谢紊乱中磷结合剂和维生素D的使用情况。
根据预先定义的纳入标准，在基线时没有患者达到iPTH和CaxP的联合目标标准。初始iPTH和CaxP的平均值分别为530.0±134.3 pg/mL和4.82 mmol²/L²（平均值±标准差）。尽管存在不利的预后因素，但25%的入选患者在试验结束时达到了联合目标。每位患者iPTH的平均降低值为203.6 pg/mL [95%置信区间（CI）183.3 - 224.0]，CaxP为0.69 mmol²/L² [95%-CI 0.57 - 0.79]。Ca和P分别降低了5.3% [95%-CI 4.3 - 6.3]和5.5% [95%-CI 3.4 - 7.7]。试验结束时西那卡塞的平均日剂量为44.9±25.0 mg（平均值±标准差）。在基线时，接受疗效分析的患者中90%（n = 500/555）使用了磷结合剂，57%（n = 317/555）使用了钙基磷结合剂。59%的患者（n = 328/555）记录使用了活性维生素D（所有活性维生素D化合物）。在试验过程中未观察到这些治疗方法有相关变化。西那卡塞的耐受性良好，913例入选患者中有57例（6%）记录了94例药物不良反应。
四分之一的患者在治疗6个月后使用相对低剂量的西那卡塞达到了iPTH和CaxP的联合目标。iPTH、Ca和P均有所降低。结果证实了西那卡塞在治疗sHPT方面的高效性，并强调了西那卡塞在控制Ca和P方面的作用。
