Randomized Clinical Trial Design to Assess Abatacept in Resistant Nephrotic Syndrome.
Randomized Clinical Trial Design to Assess Abatacept in Resistant Nephrotic Syndrome.
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DOI：
10.1016/j.ekir.2017.08.013
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发表时间：
2018-01
影响因子：
6
通讯作者：
Greka A
中科院分区：
文献类型：
--
作者：
Trachtman H;Gipson DS;Somers M;Spino C;Adler S;Holzman L;Kopp JB;Sedor J;Overfield S;Elegbe A;Maldonado M;Greka A
难治性肾病综合征是一种罕见的肾小球疾病，发生在儿童和成人。没有食品和药物管理局批准的治疗方法能够持续缓解蛋白尿和保护肾功能。CD 80（B7-1）可以在受损的足细胞上表达，并且阿巴西普（基于CD 80的天然配体的修饰的CTLA 4-IG）的施用与实验和临床环境中尿蛋白排泄的持续正常化和肾小球滤过率的维持相关。在这份报告中，我们描述了阿巴西普治疗局灶节段性肾小球硬化或微小病变所致难治性肾病综合征患者的随机、安慰剂对照临床试验的基本原理和设计。该设计是平行组和交叉设计（crossover design，简称crossover）的混合，主要目的在研究的第一阶段进行评估，次要目的使用两个阶段的数据进行评估。所有受试者将在其中一个阶段接受活性药物。每个周期的治疗持续时间为4个月。主要结局将是肾病范围蛋白尿改善至亚肾病范围，即从基线至4个月尿蛋白：肌酐比值降低≥ 50%并降低至< 3。预计样本量为90例患者，具有80%的把握度检测到28%的治疗差异。这项研究推进了验证CD 80作为难治性肾病综合征治疗靶点的努力，并对这种严重的肾脏疾病实施了一种基于精确医学的方法，其中治疗药物的选择由个体患者的潜在疾病机制指导。
Treatment-resistant nephrotic syndrome is a rare form of glomerular disease that occurs in children and adults. No Food and Drug Administration−approved treatments consistently achieve remission of proteinuria and preservation of kidney function. CD80 (B7-1) can be expressed on injured podocytes, and administration of abatacept (modified CTLA4-Ig based on a natural ligand to CD80) has been associated with sustained normalization of urinary protein excretion and maintenance of glomerular filtration rate in experimental and clinical settings. In this report, we describe the rationale for and design of a randomized, placebo-controlled, clinical trial of abatacept in patients with treatment-resistant nephrotic syndrome caused by focal segmental glomerulosclerosis or minimal change disease. The design is a hybrid of a parallel-group and crossover design (switchover) with the primary objectives assessed in the first period of the study and the secondary objectives assessed using data from both periods. All participants will receive the active agent in 1 of the periods. The duration of treatment will be 4 months per period. The primary outcome will be improvement in nephrotic-range proteinuria to subnephrotic range, that is, reduction from baseline to 4 months in urine protein:creatinine ratio ≥ 50% and to a level < 3. The projected sample size is 90 patients, which has 80% power to detect a treatment difference of 28%. This study advances efforts to validate CD80 as a therapeutic target for treatment-resistant nephrotic syndrome, and implements a precision medicine-based approach to this serious kidney condition in which the selection of a therapeutic agent is guided by the underlying disease mechanism operating in individual patients.
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影响因子：
18.2
作者：
Greka A;Mundel P
通讯作者：
Mundel P
DOI：
10.1056/nejmoa1304572
发表时间：
2013-12-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Yu CC;Fornoni A;Weins A;Hakroush S;Maiguel D;Sageshima J;Chen L;Ciancio G;Faridi MH;Behr D;Campbell KN;Chang JM;Chen HC;Oh J;Faul C;Arnaout MA;Fiorina P;Gupta V;Greka A;Burke GW 3rd;Mundel P
通讯作者：
Mundel P
影响因子：
32.4
作者：
Esensten JH;Helou YA;Chopra G;Weiss A;Bluestone JA
通讯作者：
Bluestone JA
影响因子：
158.5
作者：
Genovese, MC;Becker, J;Dougados, M
通讯作者：
Dougados, M
影响因子：
15.9
作者：
Reiser, J;von Gersdorff, G;Mundel, P
通讯作者：
Mundel, P