Vadadustat Three Times Weekly in Patients With Anemia Due to Dialysis-Dependent CKD.

The objective of this study was to investigate the efficacy and safety of conversion from the long-acting ESA methoxy polyethylene glycol-epoetin-ß (MPG-EPO) to the oral HIF-PHI vadadustat 3 times weekly versus maintenance therapy with MPG-EPO.

本研究的目的是研究从长效促红细胞生成剂甲氧聚乙二醇-依泊汀-ß（MPG-EPO）转换为口服HIF-PHI vadadustat每周三次治疗与继续使用MPG-EPO维持治疗的有效性和安全性。

intervention

Participants were randomized 1:1:1 to vadadustat at a starting dose of 600mg thrice weekly, vadadustat at a starting dose of 900mg thrice weekly, or MPG-EPO for up to 52 treatment weeks and 4 safety follow-up weeks after the end of treatment or early termination.

参与者被随机分为1:1:1，分别接受初始剂量为每周三次600mg的 vadadustat，初始剂量为每周三次900mg的 vadadustat，或 MPG-EPO，治疗周期最多为52周，并在治疗结束或提前终止后进行最多4周的安全随访。

outcomes

Primary and secondary efficacy end points were the mean change in hemoglobin concentration from baseline during primary (weeks 20-26) and secondary (weeks 46-52) evaluation periods, respectively.

主要和次要疗效终点分别是基线期间血红蛋白浓度的平均变化，在主要评估期（第20-26周）和次要评估期（第46-52周）分别进行评估。

Noninferiority was specified as a lower bound of the 95% CI above -0.75g/dL for the difference in mean change in hemoglobin concentration from baseline.

非劣效性被定义为95%置信区间下限高于基线血红蛋白浓度平均变化差异的-0.75g/dL。

Other efficacy end points were the proportion of participants with hemoglobin levels within the target range and the proportions of participants requiring ESA or red blood cell transfusion rescue for anemia during the evaluation periods.

其他疗效终点包括在目标范围内血红蛋白水平的参与者比例，以及在评估期间需要使用红细胞生成素(ESA)或红细胞输血救治贫血的参与者比例。

Primary safety end points were any treatment-emergent and serious adverse events (AEs).

主要的安全终点是任何治疗后出现的和严重的不良事件(AEs)。

Results

After combining the vadadustat groups (600mg and 900mg thrice weekly; n=304), vadadustat was noninferior to MPG-EPO (n=152) for primary (least-squares mean treatment difference, -0.33; 95% CI, -0.53 to-0.13) and secondary (-0.33; -0.56 to-0.09) efficacy end points.

将 vadadustat 组（每周三次，600mg 和 900mg；n=304）合并后，vadadustat 在主要（最小二乘平均治疗差异，-0.33；95% 置信区间，-0.53 至 -0.13）和次要（-0.33；-0.56 至 -0.09）疗效终点上对 MPG-EPO（n=152）非劣效。

Mean hemoglobin concentrations were stable for all groups except for an initial slight decrease in the vadadustat 600mg group, which stabilized by week 12.

所有组的平均血红蛋白浓度保持稳定，除了 vadadustat 600mg 组最初略有下降，但到第12周时稳定。

ESA rescue for anemia was more frequent in the MPG-EPO group (primary evaluation period, 27.7%; secondary evaluation period, 16.2%) than in the combined vadadustat (14.2%; 7.3%) groups.

ESA救援治疗贫血在MPG-EPO组中更为频繁（主要评估期为27.7%；次要评估期为16.2%），而在联合vadadustat组中较低（分别为14.2%和7.3%）

Transfusion rates were low and occurred at similar rates across treatment groups (2.7% and 4.0% in the combined vadadustat and MPG-EPO groups, respectively).

输血率较低，各治疗组之间发生率相似（联合vadadustat组为2.7%，MPG-EPO组为4.0%）

The incidences of any treatment-emergent and serious treatment-emergent AEs were similar across treatment groups.

各治疗组中，任何治疗相关和严重治疗相关不良事件的发生率相似。

limitations

Potential errors in attribution of AEs as drug-related.

将不良事件归因于药物相关的潜在错误。

Conclusions

Three-times-weekly vadadustat was noninferior to MPG-EPO in its effect on hemoglobin levels without detectable differences in AEs.

每周三次的 vadadustat 在对血红蛋白水平的影响上不劣于 MPG-EPO，且在不良事件（AEs）上没有可检测到的差异。

funding

Funding from a private entity (Akebia Therapeutics, Inc).

资金来自私营实体（Akebia Therapeutics, Inc）。

trial_registration

Registered at ClinicalTrials.gov with study identifier NCT04707768.

该研究已在ClinicalTrials.gov注册，研究标识为NCT04707768。

PLAIN-LANGUAGE SUMMARY: Vadadustat, taken 3 times a week, was noninferior to methoxy polyethylene glycol-epoetin-ß (MPG-EPO) in treating anemia.

简易语言摘要：每周三次服用Vadadustat在治疗贫血方面与甲氧聚乙二醇-依泊汀-ß（MPG-EPO）相当。

Vadadustat is an oral drug used to treat anemia in people with chronic kidney disease.

Vadadustat是一种口服药物，用于治疗慢性肾脏病患者的贫血。

This study enrolled participants undergoing dialysis for kidney failure and compared the efficacy and safety of continuing to receive MPG-EPO, a long-acting injectable anemia treatment, or switching to vadadustat, taken by mouth 3 times per week for 1 year.

该研究招募了接受透析治疗肾衰竭的参与者，并比较了继续接受MPG-EPO（一种长效注射性贫血治疗药物）或改用vadadustat（每周口服三次，持续一年）的疗效和安全性。

Vadadustat was noninferior to MPG-EPO in maintaining hemoglobin levels.

Vadadustat 在维持血红蛋白水平方面与 MPG-EPO 相当。

Hemoglobin levels remained stable across all groups, except for a slight decrease in the lower-dose vadadustat group, which stabilized with dose titration by week 12.

所有组的血红蛋白水平保持稳定，除了低剂量 vadadustat 组略有下降，但通过第12周的剂量调整后稳定。

The occurrence of new or serious side effects was similar across treatment groups.

新发或严重副作用的发生在各治疗组之间相似。