{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:16:17Z","timestamp":1792444577479,"version":"4.5.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","funder":[{"name":"Reata Pharmaceuticals"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2022,12]]},"abstract":"\n Background and objectives<\/jats:title>\n Alport syndrome is an inherited disease characterized by progressive loss of kidney function. We aimed to evaluate the safety and efficacy of bardoxolone methyl in patients with Alport syndrome.<\/jats:p>\n <\/jats:sec>\n \n Design, setting, participants, & measurements<\/jats:title>\n \n We randomly assigned patients with Alport syndrome, ages 12\u201370 years and eGFR 30\u201390 ml\/min per 1.73 m\n 2<\/jats:sup>\n , to bardoxolone methyl (\n n<\/jats:italic>\n =77) or placebo (\n n<\/jats:italic>\n =80). Primary efficacy end points were change from baseline in eGFR at weeks 48 and 100. Key secondary efficacy end points were change from baseline in eGFR at weeks 52 and 104, after an intended 4 weeks off treatment. Safety was assessed by monitoring for adverse events and change from baseline in vital signs, 12-lead electrocardiograms, laboratory measurements (including, but not limited to, aminotransferases, urinary albumin-creatinine ratio, magnesium, and B-type natriuretic peptide), and body weight.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Patients randomized to bardoxolone methyl experienced preservation in eGFR relative to placebo at 48 and 100 weeks (between-group differences: 9.2 [97.5% confidence interval, 5.1 to 13.4;\n P<\/jats:italic>\n <0.001] and 7.4 [95% confidence interval, 3.1 to 11.7;\n P<\/jats:italic>\n =0.0008] ml\/min per 1.73 m\n 2<\/jats:sup>\n , respectively). After a 4-week off-treatment period, corresponding mean differences in eGFR were 5.4 (97.5% confidence interval, 1.8 to 9.1;\n P<\/jats:italic>\n <0.001) and 4.4 (95% confidence interval, 0.7 to 8.1;\n P<\/jats:italic>\n =0.02) ml\/min per 1.73 m\n 2<\/jats:sup>\n at 52 and 104 weeks, respectively. In a\n post hoc<\/jats:italic>\n analysis with no imputation of missing eGFR data, the difference at week 104 was not statistically significant (1.5 [95% confidence interval, \u22121.9 to 4.9] ml\/min per 1.73 m\n 2<\/jats:sup>\n ). Discontinuations from treatment were more frequent among patients randomized to bardoxolone methyl; most discontinuations were due to protocol-specified criteria being met for increases in serum transaminases. Serious adverse events were more frequent among patients randomized to placebo. Three patients in each group developed kidney failure.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n In adolescent and adult patients with Alport syndrome receiving standard of care, treatment with bardoxolone methyl resulted in preservation in eGFR relative to placebo after a 2-year study period; off-treatment results using all available data were not significantly different.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial registry name and registration number:<\/jats:title>\n A Phase 2\/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients with Alport Syndrome - CARDINAL (CARDINAL), NCT03019185<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.02400222","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T15:50:11Z","timestamp":1669045811000},"page":"1763-1774","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":46,"title":["Effects of Bardoxolone Methyl in Alport Syndrome"],"prefix":"10.2215","volume":"17","clinical-trial-number":[{"clinical-trial-number":"nct03019185","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1812-6587","authenticated-orcid":false,"given":"Bradley A.","family":"Warady","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Pediatrics, Children\u2019s Mercy Kansas City, Kansas City, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo E.","family":"Pergola","sequence":"additional","affiliation":[{"name":"Renal Associates PA, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-7100","authenticated-orcid":false,"given":"Rajiv","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine and Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Andreoli","sequence":"additional","affiliation":[{"name":"Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald B.","family":"Appel","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sripal","family":"Bangalore","sequence":"additional","affiliation":[{"name":"Cardiovascular Clinical Research Center, New York University School of Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey A.","family":"Block","sequence":"additional","affiliation":[{"name":"Department of Clinical Research and Medical Affairs, US Renal Care, Inc., Plano, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlene B.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Section of Nephrology, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie P.","family":"Chin","sequence":"additional","affiliation":[{"name":"Reata Pharmaceuticals, Plano, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisha L.","family":"Gibson","sequence":"additional","affiliation":[{"name":"University of North Carolina Kidney Center at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angie","family":"Goldsberry","sequence":"additional","affiliation":[{"name":"Reata Pharmaceuticals, Plano, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumoto","family":"Iijima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley A.","family":"Inker","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Tufts Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford E.","family":"Kashtan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Department of Pediatrics, Alport Syndrome Treatments and Outcomes Registry, University of Minnesota Medical School and Masonic Children\u2019s Hospital, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Knebelmann","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Necker Hospital, Assistance Publique-H\u00f4pitaux de Paris, University of Paris Cit\u00e8, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura H.","family":"Mariani","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin J.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Reata Pharmaceuticals, Plano, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kandai","family":"Nozu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"O\u2019Grady","sequence":"additional","affiliation":[{"name":"Reata Pharmaceuticals, Plano, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2494-3970","authenticated-orcid":false,"given":"Michelle N.","family":"Rheault","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Department of Pediatrics, Alport Syndrome Treatments and Outcomes Registry, University of Minnesota Medical School and Masonic Children\u2019s Hospital, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold L.","family":"Silva","sequence":"additional","affiliation":[{"name":"Boise Kidney and Hypertension Institute, Meridian, Idaho"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Stenvinkel","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science, Technology and Intervention, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8714-2332","authenticated-orcid":false,"given":"Roser","family":"Torra","sequence":"additional","affiliation":[{"name":"Inherited Kidney Disorders, Nephrology Department, Fundacio Puigvert, IIB Sant Pau, REDINREN (Instituto de Investigacion Carlos III), Universitat Autonoma de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7599-0534","authenticated-orcid":false,"given":"Glenn M.","family":"Chertow","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,12]]},"reference":[{"key":"B1-20241015","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nrneph.2012.259","article-title":"Alport syndrome--Insights from basic and clinical research","volume":"9","author":"Kruegel","year":"2013","journal-title":"Nat Rev Nephrol"},{"key":"B2-20241015","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1681\/ASN.V114649","article-title":"X-linked Alport syndrome: Natural history in 195 families and genotype- phenotype correlations in 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History"}},{"value":"2022-10-19","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}