Global Phase 3 programme of vadadustat for treatment of anaemia of chronic kidney disease: rationale, study design and baseline characteristics of dialysis-dependent patients in the INNO2VATE trials.
Global Phase 3 programme of vadadustat for treatment of anaemia of chronic kidney disease: rationale, study design and baseline characteristics of dialysis-dependent patients in the INNO2VATE trials.
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DOI：
10.1093/ndt/gfaa204
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发表时间：
2021-11-09
期刊：
影响因子：
--
通讯作者：
Chertow GM
中科院分区：
文献类型：
--
作者：
Eckardt KU;Agarwal R;Farag YM;Jardine AG;Khawaja Z;Koury MJ;Luo W;Matsushita K;McCullough PA;Parfrey P;Ross G;Sarnak MJ;Vargo D;Winkelmayer WC;Chertow GM
红细胞生成刺激剂（ESA）是目前治疗慢性肾脏病（CKD）贫血的主要药物。Vadadustat是一种研究性口服低氧诱导因子脯氨酰羟化酶抑制剂，可刺激内源性促红细胞生成素的形成。INNO 2 VATE项目包括两项研究，旨在评价vadadustat与ESA darbepostatin alfa在改善透析依赖性CKD（DD-CKD）患者贫血方面的安全性和疗效。在此，我们描述了试验设计沿着患者人口统计学和基线特征。两项III期、开放标签、双盲、活性对照试验入组了近期开始透析且ESA暴露有限（偶发DD-CKD试验）或正在接受ESA治疗维持透析（流行DD-CKD试验）的CKD贫血成人患者。研究阶段包括纠正/转换（第0-23周）、维持（第24-52周）、长期治疗（第53周至治疗结束）和安全性随访。主要安全性终点是至首次发生重大不良心血管事件的时间，主要疗效终点是血红蛋白的变化（基线至第24-36周）。分别有369例和3554例患者在偶发DD-CKD和现患DD-CKD试验中接受随机化。两项试验中患者的人口统计学和基线特征相似，与DD-CKD中通常观察到的相似。这两项INNO 2 VATE试验将提供关于一种新型贫血管理方法在不同DD-CKD人群中的安全性和疗效的重要信息。入组患者的人口统计学和基线特征表明，研究结果将代表大部分DD-CKD人群。
Erythropoiesis-stimulating agents (ESAs) are currently the mainstay of treatment for anaemia of chronic kidney disease (CKD). Vadadustat is an investigational oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that stimulates endogenous erythropoietin formation. The INNO2VATE programme comprises two studies designed to evaluate the safety and efficacy of vadadustat versus the ESA darbepoetin alfa in ameliorating anaemia in patients with dialysis-dependent CKD (DD-CKD). Here we describe the trial design along with patient demographics and baseline characteristics. Two Phase 3, open-label, sponsor-blind, active-controlled trials enrolled adults with anaemia of CKD who recently initiated dialysis and had limited ESA exposure (incident DD-CKD trial) or were receiving maintenance dialysis with ESA treatment (prevalent DD-CKD trial). Study periods include correction/conversion (Weeks 0–23), maintenance (Weeks 24–52), long-term treatment (Weeks 53 to end of treatment) and safety follow-up. The primary safety endpoint is the time to the first major adverse cardiovascular event and the primary efficacy endpoint is the change in haemoglobin (baseline to Weeks 24–36). A total of 369 and 3554 patients were randomized in the incident DD-CKD and prevalent DD-CKD trials, respectively. Demographics and baseline characteristics were similar among patients in both trials and comparable to those typically observed in DD-CKD. The two INNO2VATE trials will provide important information on the safety and efficacy of a novel approach for anaemia management in a diverse DD-CKD population. Demographics and baseline characteristics of enrolled patients suggest that study results will be representative for a large proportion of the DD-CKD population.
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DOI：
10.1056/nejmoa1306033
发表时间：
2013-12-26
期刊：
The New England journal of medicine
影响因子：
--
作者：
de Zeeuw D;Akizawa T;Audhya P;Bakris GL;Chin M;Christ-Schmidt H;Goldsberry A;Houser M;Krauth M;Lambers Heerspink HJ;McMurray JJ;Meyer CJ;Parving HH;Remuzzi G;Toto RD;Vaziri ND;Wanner C;Wittes J;Wrolstad D;Chertow GM;BEACON Trial Investigators
通讯作者：
BEACON Trial Investigators
影响因子：
13.6
作者：
Babitt, Jodie L.;Lin, Herbert Y.
通讯作者：
Lin, Herbert Y.
影响因子：
7.4
作者：
Haase VH
通讯作者：
Haase VH
CKD 中红细胞生成刺激剂的剂量和不良后果：荟萃回归分析。
DOI：
10.1053/j.ajkd.2012.07.014
发表时间：
2013-01
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Koulouridis I;Alfayez M;Trikalinos TA;Balk EM;Jaber BL
通讯作者：
Jaber BL
影响因子：
4.2
作者：
McCullough, Peter A.;Barnhart, Huiman X.;Califf, Robert M.
通讯作者：
Califf, Robert M.