柠檬酸铁对中国血液透析慢性肾脏病患者高磷血症的疗效和安全性：一项III期多中心随机开放标签活性药物对照研究。

Efficacy and Safety of Ferric Citrate on Hyperphosphatemia among Chinese Patients with Chronic Kidney Disease Undergoing Hemodialysis: A Phase III Multicenter Randomized Open-Label Active-Drug-Controlled Study.

作者信息

Wang Yong, Chen Xiangmei, Zhu Hanyu, Guo Zhiyong, Yang Yibin, Luo Ping, He Yani, Xu Yan, Ji Daxi, Gao Xinlu, Sun Xiuli, Xing Changying, Wang Yu, Wang Xiaohui, Zhao Shuping, Guan Yan, Lin Hongli, Zhong Aimin, Shui Hua, Shao Fengmin, Lv Lu, Yan Yuehong, Sun Xiaokun, Zhang Lei

机构信息

Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China.

Department of Nephrology, Changhai Hospital of Shanghai, Naval Medical University, Shanghai, China.

出版信息

Am J Nephrol. 2023;54(11-12):479-488. doi: 10.1159/000534484. Epub 2023 Oct 9.

DOI:10.1159/000534484

PMID:37812931

Abstract

INTRODUCTION

Hyperphosphatemia in chronic kidney disease (CKD) patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis.

METHODS

Chinese patients undergoing hemodialysis were randomized into two treatment groups in a 1:1 ratio, receiving either ferric citrate or sevelamer carbonate, respectively, for 12 weeks. Serum phosphorus levels, calcium concentration, and iron metabolism parameters were evaluated every 2 weeks. Frequency and severity of adverse events were recorded.

RESULTS

217 (90.4%) patients completed the study with balanced demographic and baseline characteristics between two groups. Ferric citrate decreased the serum phosphorus level to 0.59 ± 0.54 mmol/L, comparable to 0.56 ± 0.62 mmol/L by sevelamer carbonate. There was no significant difference between two groups (p > 0.05) in the proportion of patients with serum phosphorus levels reaching the target range, the response rate to the study drug, and the changes of corrected serum calcium concentrations, and intact-PTH levels at the end of treatment. The change of iron metabolism indicators in the ferric citrate group was significantly higher than those in the sevelamer carbonate group. There are 47 (40.5%) patients in the ferric citrate group, and 26 (21.3%) patients in the sevelamer carbonate group experienced drug-related treatment emergent adverse events (TEAEs); most were mild and tolerable. Common drug-related TEAEs were gastrointestinal disorders, including diarrhea (12.9 vs. 2.5%), fecal discoloration (14.7 vs. 0%), and constipation (1.7 vs. 7.4%) in ferric citrate and sevelamer carbonate group.

CONCLUSION

Ferric citrate capsules have good efficacy and safety in the control of hyperphosphatemia in adult patients with CKD undergoing hemodialysis. Efficacy is not inferior to sevelamer carbonate. The TEAEs were mostly mild and tolerated by the patients.

摘要

引言

慢性肾脏病（CKD）患者的高磷血症与死亡率呈正相关。柠檬酸铁是一种有效的磷结合剂，可降低血清磷水平并改善铁代谢。我们在中国接受血液透析的CKD患者中比较了其与活性药物的疗效和安全性。

方法

接受血液透析的中国患者按1:1比例随机分为两个治疗组，分别接受柠檬酸铁或碳酸司维拉姆治疗12周。每2周评估血清磷水平、钙浓度和铁代谢参数。记录不良事件的发生频率和严重程度。

结果

217名（90.4%）患者完成了研究，两组间人口统计学和基线特征均衡。柠檬酸铁将血清磷水平降至0.59±0.54 mmol/L，与碳酸司维拉姆的0.56±0.62 mmol/L相当。两组在血清磷水平达到目标范围的患者比例、对研究药物的反应率以及治疗结束时校正血清钙浓度和完整甲状旁腺激素水平的变化方面无显著差异（p>0.05）。柠檬酸铁组铁代谢指标的变化明显高于碳酸司维拉姆组。柠檬酸铁组有47名（40.5%）患者，碳酸司维拉姆组有26名（21.3%）患者发生与药物相关的治疗突发不良事件（TEAE）；大多数为轻度且可耐受。常见的与药物相关的TEAE是胃肠道疾病，柠檬酸铁组和碳酸司维拉姆组分别为腹泻（12.9%对2.5%）、粪便变色（14.7%对0%）和便秘（1.7%对7.4%）。