[German observational trial on secondary hyperparathyroidism therapy with cinacalcet (EARLY)]

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.