Head-to-head comparison of the new calcimimetic agent evocalcet with cinacalcet in Japanese hemodialysis patients with secondary hyperparathyroidism
Head-to-head comparison of the new calcimimetic agent evocalcet with cinacalcet in Japanese hemodialysis patients with secondary hyperparathyroidism
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DOI：
10.1016/j.kint.2018.05.013
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发表时间：
2018-10-01
影响因子：
19.6
通讯作者：
Akizawa, Tadao
中科院分区：
文献类型：
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作者：
Fukagawa, Masafumi;Shimazaki, Ryutaro;Akizawa, Tadao
继发性甲状旁腺功能亢进（SHPT）导致心血管钙化，影响慢性肾脏疾病患者的生存和生活质量。西那卡塞用于控制SHPT，但它可能诱发胃肠道症状，导致依从性降低和剂量不足。因此，需要开发引起较少胃肠道症状的新的拟钙剂。在此，我们进行了一项III期、随机、双盲、双模拟试验，以头对头比较evocalcet（一种新的口服拟钙剂）与已确立的西那卡塞的疗效和安全性。接受血液透析的SHPT日本患者随机接受evocalcet或西那卡塞（各317例患者）治疗30周。主要有效性终点是在第28 - 30周达到平均全段甲状旁腺激素水平60 - 240 pg/mL的患者比例方面，evocalcet非劣效于西那卡塞（非劣效性界值，-15%，符合方案集分析）。在evocalcet和西那卡塞组中，分别有72.7%和76.7%的患者达到了目标全段甲状旁腺激素水平（非劣效性组间差异：-4.0% [95%置信区间-11.4%，3.5%]）。胃肠道相关不良事件的发生率分别为18.6%和32.8%（组间差异：-14.2% [-20.9%，-7.5%]，具有显著优效性）。因此，证明了evocalcet在抑制全段甲状旁腺激素方面非劣效于西那卡塞，胃肠道相关不良事件较少。因此，evocalcet可能是一个有利的替代现有的拟钙治疗SHPT。
Secondary hyperparathyroidism (SHPT) leads to cardiovascular calcification, which affects survival and quality of life in patients with chronic kidney disease. Cinacalcet is used to control SHPT, but it may induce gastrointestinal symptoms, resulting in lower adherence and insufficient dosages. Therefore, a need exists to develop new calcimimetics that cause fewer gastrointestinal symptoms. Here we conducted a phase 3, randomized, double-blind, double-dummy trial for a head to-head comparison of the efficacy and safety of evocalcet, a new oral calcimimetic, to the established cinacalcet. Japanese patients with SHPT on hemodialysis were randomized to receive evocalcet or cinacalcet (317 patients each) for 30 weeks. The primary efficacy endpoint was non-inferiority of evocalcet to cinacalcet in the proportion of patients achieving a mean intact parathyroid hormone level of 60 to 240 pg/mL from week 28 to 30 (non inferiority margin, -15%, per protocol set analyses). In the evocalcet and cinacalcet groups, 72.7% and 76.7%, respectively, achieved the target intact parathyroid hormone level (between-group difference: -4.0% [95% confidence interval -11.4%, 3.5%], for non-inferiority). The incidence of gastrointestinal-related adverse events was 18.6% and 32.8%, respectively (between-group difference: -14.2% [-20.9%, -7.5%], significant for superiority). Thus, the non-inferiority of evocalcet to cinacalcet in suppressing intact parathyroid hormone with fewer gastrointestinal-related adverse events was demonstrated. Hence, evocalcet may be a favorable alternative to existing calcimimetics for management of SHPT.