{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:40:00Z","timestamp":1788921600301,"version":"build-2803163510"},"reference-count":15,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The SONAR trial uses an enrichment design based on the individual response to the selective endothelin receptor antagonist atrasentan on efficacy (the degree of the individual response in the urinary albumin\u2010to\u2010creatinine ratio [UACR]) and safety\/tolerability (signs of sodium retention and acute increases in serum creatinine) to assess the effects of this agent on major renal outcomes. The patient population and enrichment results are described here.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients with type 2 diabetes with an estimated glomerular filtration rate (eGFR) within 25 to 75\u2009mL\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      and UACR between 300 and 5000\u2009mg\/g were enrolled. After a run\u2010in period, eligible patients received 0.75\u2009mg\/d of atrasentan for 6\u2009weeks. A total of 2648 responder patients in whom UACR decreased by \u226530% compared to baseline were enrolled, as were 1020 non\u2010responders with a UACR decrease of &lt;30%. Patients who experienced a weight gain of &gt;3\u2009kg and in whom brain natriuretic peptide exceeded \u2265300\u2009pg\/mL, or who experienced an increase in serum creatinine &gt;20% (0.5\u2009mg\/dL), were not randomized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Baseline characteristics were similar for atrasentan responders and non\u2010responders. Upon entry to the study, median UACR was 802\u2009mg\/g in responders and 920\u2009mg\/g in non\u2010responders. After 6\u2009weeks of treatment with atrasentan, the UACR change in responders was \u221248.8% (95% CI, \u221249.8% to \u221247.9%) and in non\u2010responders was \u22121.2% (95% CI, \u22126.4% to 3.9%). Changes in other renal risk markers were similar between responders and non\u2010responders except for a marginally greater reduction in systolic blood pressure and eGFR in responders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The enrichment period has successfully identified a population with a profound UACR reduction without clinical signs of sodium retention in whom a large atrasentan effect on clinically important renal outcomes is possible. The SONAR trial aims to establish whether atrasentan confers renal protection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13315","type":"journal-article","created":{"date-parts":[[2018,3,31]],"date-time":"2018-03-31T11:04:12Z","timestamp":1522494252000},"page":"1829-1835","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Baseline characteristics and enrichment results from the\n                    <scp>SONAR<\/scp>\n                    trial"],"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1183-1267","authenticated-orcid":false,"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":"Fan Fan","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, 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":"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6317-3975","authenticated-orcid":false,"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 New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheldon","family":"Tobe","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology Sunnybrook Health Sciences Centre, University of Toronto and the Northern Ontario School of Medicine  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Wigderson","sequence":"additional","affiliation":[{"name":"Pharma Development AbbVie  North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Yi","sequence":"additional","affiliation":[{"name":"Pharma Development AbbVie  North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Henrik","family":"Parving","sequence":"additional","affiliation":[{"name":"Department of Medical Endocrinology Rigshospitalet, University of Copenhagen  Copenhagen Denmark"},{"name":"Faculty of Health Science Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dick","family":"de Zeeuw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)30045-6"},{"key":"e_1_2_6_3_1","article-title":"Renal trials in diabetes need a platform: time for a global approach?","author":"Zeeuw D","year":"2017","journal-title":"Lancet Diabetes 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