{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T01:53:50Z","timestamp":1788054830211,"version":"build-2784847793"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,3,9]],"date-time":"2018-03-09T00:00:00Z","timestamp":1520553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Individuals with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin\u2010to\u2010creatinine ratio (UACR), with a large variability between patients. We are assessing its effect on renal outcomes in the Study Of diabetic Nephropathy with AtRasentan (SONAR; NCT01858532) with an enrichment design (&gt;30% lowering of albuminuria) to select patients most likely to benefit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>SONAR is a randomized, double\u2010blind, placebo\u2010controlled trial with approximately 3500 participants who have stage 2\u20134 CKD and macroalbuminuria and are receiving a maximum tolerated dose of a renin\u2010angiotensin system inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After 6\u2009weeks of exposure to atrasentan 0.75\u2009mg once daily (enrichment period), participants with \u226530% UACR decrease and no tolerability issues (responders) were randomly assigned to placebo or atrasentan 0.75\u2009mg\/day. The responder group will be used for primary efficacy and safety analyses. Approximately 1000 participants with &lt;30% UACR reduction (non\u2010responders) were also randomized to placebo or atrasentan. The primary endpoint is a composite of a sustained doubling of serum creatinine or end\u2010stage renal disease. The original power calculation indicated that a total of 425 primary renal events in the responder group provides 90% power to detect a 27% reduction in relative risk (alpha level of .05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SONAR aims to determine whether atrasentan added to guideline\u2010recommended therapies safely reduces the risk of CKD progression and delays the onset of end\u2010stage renal disease in patients with type 2 diabetes and nephropathy. SONAR also aims to establish whether the enrichment of patients based on their initial \u201csurrogate\u201d response to atrasentan will deliver a trial design in accord with personalized treatment of diabetic kidney disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13245","type":"journal-article","created":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T06:42:43Z","timestamp":1517899363000},"page":"1369-1376","source":"Crossref","is-referenced-by-count":63,"title":["Rationale and protocol of the Study Of diabetic Nephropathy with AtRasentan (SONAR) trial: A clinical trial design novel to diabetic nephropathy"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J. L.","family":"Heerspink","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis L.","family":"Andress","sequence":"additional","affiliation":[{"name":"Pharma Development, AbbVie  North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Bakris","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Endocrinology, ASH Comprehensive Hypertension Center University of Chicago Medicine and Biological Sciences  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Brennan","sequence":"additional","affiliation":[{"name":"Pharma Development, AbbVie  North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Correa\u2010Rotter","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Mineral Metabolism, National Medical Science and Nutrition Institute Salvador Zubir\u00e1n  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyotirmoy","family":"Dey","sequence":"additional","affiliation":[{"name":"Pharma Development, AbbVie  North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan Fan","family":"Hou","sequence":"additional","affiliation":[{"name":"Division of Nephrology Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalane W.","family":"Kitzman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Wake Forest School of Medicine  Winston\u2010Salem North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Kohan","sequence":"additional","affiliation":[{"name":"Division of Nephrology University of Utah Health Sciences Center  Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Makino","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University  Okayama\u2010Shi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"McMurray","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Research Centre University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlado","family":"Perkovic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine George Institute for Global Health, UNSW Sydney  Newtown 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