斯帕森坦与伊尔贝沙坦在焦点细分细胞凝结症中的对比
Michelle N Rheault1, Charles E Alpers1, Jonathan Barratt1
1From the Division of Pediatric Nephrology, University of Minnesota Medical School, Minneapolis (M.N.R.); the Department of Laboratory Medicine and Pathology, University of Washington, Seattle (C.E.A.); the Department of Cardiovascular Sciences, University of Leicester General Hospital, Leicester, United Kingdom (J.B.); Travere Therapeutics, San Diego, CA (S.B., U.D., J.K.I., R.K., W.R.); the Division of Nephrology, Columbia University Irving Medical Center, New York (P.C., J.R.); the Division of Nephrology, Department of Internal Medicine, Seoul Red Cross Hospital, Seoul, South Korea (D.-W.C.); Penn Renal Electrolyte and Hypertension Perelman, University of Pennsylvania, Philadelphia (G.C.); the Nephrology, Dialysis, and Transplantation Unit, University of Bari Aldo Moro, Bari, Italy (L.G.); the Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands (H.J.L.H.); the George Institute for Global Health (H.J.L.H., V.P.) and the Faculty of Medicine and Health (V.P.), University of New South Wales, Sydney, and the Department of Renal Medicine, Concord Repatriation General Hospital, and Concord Clinical School, University of Sydney, Concord, NSW (M.G.W.) - all in Australia; the Department of Medicine (Nephrology), Federal University of São Paulo (G.M.K.), and the Division of Nephrology, University of São Paulo (I.L.N.) - both in São Paulo; the Department of Internal Medicine, Division of Nephrology, School of Medicine, University of Utah, Salt Lake City (D.K.); Colorado Kidney Care, Denver (L.A.K.); Hackensack University Medical Center, Hackensack, NJ (K.L.); JAMCO Pharma Consulting, Stockholm (A.M.); the Division of Nephrology, Ohio State University Wexner Medical Center, Columbus (B.R.); Všeobecná fakultní nemocnice v Praze, Prague, Czech Republic (V.T.); the Nephrology Service, Hospital Británico de Buenos Aires, Buenos Aires (H. Trimarchi); the Renal Division, Emory University, Atlanta, and the NephroNet Clinical Trials Consortium, Lawrenceville - both in Georgia (J.T.); and the Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor (H. Trachtman).
在108周内,Sparsentan显著降低了焦点细分结核硬化症 (FSGS) 患者的蛋白尿. 然而,在斯帕森坦和伊尔贝萨坦治疗组之间,没有观察到估计的球过率 (eGFR) 下降的显著差异.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 临床药理学 临床药理学
- 淋巴细胞疾病 淋巴细胞疾病
背景情况:
- 焦点细分性淋巴结核硬化 (FSGS) 是导致脏疾病的重要原因,治疗选择有限.
- 斯帕森坦是一种双重内甲素和血管激素受体对抗剂,在FSGS第二阶段试验中显示它有望降低蛋白尿.
- 之前在FSGS中没有Sparsentan的长期疗效和安全数据.
研究的目的:
- 在FSGS患者中,评估与irbesartan相比,sparsentan的长期疗效和安全性.
- 评估斯帕森坦在108周内对蛋白尿和功能的影响.
- 为了确定斯帕森坦是否在减缓FSGS患者估计膜过率 (eGFR) 的下降方面提供了显著的益处.
主要方法:
- 一个第三阶段,随机,主动控制试验,涉及371名FSGS患者,年龄为8-75岁.
- 随机分配患者接受斯帕森坦或伊尔贝沙坦治疗108周.
- 疗效终点包括36周蛋白尿的部分缓解和108周的eGFR斜率;安全性也受到监测.
主要成果:
- 在36周后,42.0%的sparsentan患者实现了蛋白尿部分缓解,而irbesartan (P=0.009) 的患者为26.0%,这一益处持续到108周.
- 在108周的EGFR斜率上没有发现显著的群体间差异 (总斜率:0.3毫升/分钟/1.73米2/年;慢性斜率:0.9毫升/分钟/1.73米2/年).
- 斯帕森坦和伊尔贝萨坦显示出类似的安全性和不良事件频率.
结论:
- 与伊尔贝沙坦相比,Sparsentan在108周内有效降低FSGS患者的蛋白尿症.
- 尽管减少了蛋白尿症,但根据eGFR斜率测量,斯帕森坦在保护功能方面并没有比伊尔贝萨坦显著的优势.
- 类似的安全性概况表明,斯帕森坦是一种可行的FSGS治疗选择,特别是其抗蛋白尿作用.
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