一项关于特立帕肽联合磷酸盐结合剂作为维持性透析患者高磷血症双联治疗的随机试验（AMPLIFY）
A Randomized Trial of Tenapanor and Phosphate Binders as a Dual-Mechanism Treatment for Hyperphosphatemia in Patients on Maintenance Dialysis (AMPLIFY).
机构信息
Renal Associates, P.A., San Antonio, Texas.
Ardelyx, Inc., Fremont, California.
出版信息
J Am Soc Nephrol. 2021 Jun 1;32(6):1465-1473. doi: 10.1681/ASN.2020101398. Epub 2021 Mar 25.
BACKGROUND
Hyperphosphatemia is associated with cardiovascular morbidity and mortality in patients receiving maintenance dialysis. It is unknown whether combining two therapies with different mechanisms of action-tenapanor, an inhibitor of paracellular phosphate absorption, and phosphate binders-is safe and effective for the management of hyperphosphatemia in patients receiving maintenance dialysis.
METHODS
This double-blind phase 3 trial enrolled 236 patients undergoing maintenance dialysis with hyperphosphatemia (defined in this trial as serum phosphorus 5.5-10 mg/dl inclusive) despite receiving phosphate binder therapy (sevelamer, nonsevelamer, sevelamer plus nonsevelamer, or multiple nonsevelamer binders). These participants were randomly assigned to receive oral tenapanor 30 mg twice daily or placebo for 4 weeks. The primary efficacy end point was the change in serum phosphorus concentration from baseline to week 4.
RESULTS
Of the 236 randomized patients, 235 (99.6%) were included in the full analysis set; this included 116 in the tenapanor plus binder group and 119 in the placebo plus binder group. A total of 228 patients (96.6%) completed the 4-week treatment period. In the full analysis set (mean age 54.5 years, 40.9% women), patients treated with tenapanor plus binder achieved a larger mean change in serum phosphorus concentration from baseline to week 4 compared with placebo plus binder (-0.84 versus -0.19 mg/dl, <0.001). Diarrhea was the most commonly reported adverse event, resulting in study drug discontinuation in four of 119 (3.4%) and two of 116 (1.7%) patients receiving tenapanor plus binder or placebo plus binder, respectively.
CONCLUSIONS
A dual-mechanism treatment using both tenapanor and phosphate binders improved control of hyperphosphatemia in patients undergoing maintenance dialysis compared with phosphate binders alone.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
AMPLIFY, NCT03824587.
背景
高磷血症与接受维持性透析的患者的心血管发病率和死亡率相关。目前尚不清楚联合使用两种作用机制不同的治疗方法（即抑制细胞旁磷吸收的托伐普坦和磷结合剂）是否安全有效，能否用于管理接受维持性透析的高磷血症患者。
方法
这项双盲 3 期临床试验纳入了 236 例接受维持性透析且伴有高磷血症（定义为血清磷 5.5-10mg/dl 之间，包括两端值）的患者，这些患者在接受磷结合剂治疗（司维拉姆、非司维拉姆、司维拉姆联合非司维拉姆或多种非司维拉姆结合剂）的情况下仍存在高磷血症。这些患者被随机分配接受口服托伐普坦 30mg，每日 2 次，或安慰剂，疗程为 4 周。主要疗效终点为从基线到第 4 周时血清磷浓度的变化。
结果
在 236 例随机患者中，235 例（99.6%）被纳入全分析集；其中托伐普坦+结合剂组 116 例，安慰剂+结合剂组 119 例。共有 228 例（96.6%）患者完成了 4 周的治疗期。在全分析集（平均年龄 54.5 岁，40.9%为女性）中，与安慰剂+结合剂组相比，托伐普坦+结合剂组患者从基线到第 4 周时血清磷浓度的平均变化更大（-0.84 与-0.19mg/dl，<0.001）。最常见的不良事件是腹泻，导致 119 例患者中有 4 例（3.4%）和 116 例患者中有 2 例（1.7%）停止使用研究药物，分别接受托伐普坦+结合剂或安慰剂+结合剂治疗。
结论
与单独使用磷结合剂相比，使用托伐普坦联合磷结合剂的双重作用机制治疗可改善接受维持性透析患者的高磷血症控制。
临床试验注册名称和注册号
AMPLIFY，NCT03824587。
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