Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis

作者：Michelle N. Rheault, Charles E. Alpers, Jonathan Barratt, Stewart Bieler, Pietro A. Canetta, Dong‐Wan Chae, Gaia Coppock, Ulysses Diva, Loreto Gesualdo, Hiddo J.L. Heerspink, Jula K. Inrig, Gianna Mastroianni Kirsztajn, Donald E. Kohan, Radko Komers, Laura Kooienga, Kenneth V. Lieberman, Alex Mercer, Irene L. Noronha, Vlado Perkovic, Jai Radhakrishnan, William E. Rote, Brad H. Rovin, Vladimı́r Tesař, Hernán Trimarchi, James A. Tumlin, Muh Geot Wong, Howard Trachtman · 发表于：New England Journal of Medicine · 年份：2023 · DOI：10.1056/nejmoa2308550 · 被引用次数：117 · 研究领域：Renal Diseases and Glomerulopathies、Chronic Kidney Disease and Diabetes、Renal and Vascular Pathologies

An unmet need exists for focal segmental glomerulosclerosis (FSGS) treatment. In an 8-week, phase 2 trial, sparsentan, a dual endothelin–angiotensin receptor antagonist, reduced proteinuria in patients with FSGS. The efficacy and safety of longer-term treatment with sparsentan for FSGS are unknown. Download a PDF of the Research Summary. In this phase 3 trial, we enrolled patients with FSGS (without known secondary causes) who were 8 to 75 years of age; patients were randomly assigned to receive sparsentan or irbesartan (active control) for 108 weeks. The surrogate efficacy end point assessed at the prespecified interim analysis at 36 weeks was the FSGS partial remission of proteinuria end point (defined as a urinary protein-to-creatinine ratio of ≤1.5 [with protein and creatinine both measured in grams] and a >40% reduction in the ratio from baseline). The primary efficacy end point was the estimated glomerular filtration rate (eGFR) slope at the time of the final analysis. The change in eGFR from baseline to 4 weeks after the end of treatment (week 112) was a secondary end point. Safety was also evaluated. A total of 371 patients underwent randomization: 184 were assigned to receive sparsentan and 187 to receive irbesartan. At 36 weeks, the percentage of patients with partial remission of proteinuria was 42.0% in the sparsentan group and 26.0% in the irbesartan group (P=0.009), a response that was sustained through 108 weeks. At the time of the final analysis at week 108, t...