{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:04:20Z","timestamp":1791475460232,"version":"4.3.4"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","award":["NCT02969655"],"award-info":[{"award-number":["NCT02969655"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates genes related to iron metabolism. The efficacy (noninferiority) and safety of daprodustat compared with standard therapy (darbepoetin alfa) was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>\n                      This was a randomized, phase 3, double-blind, active-control study in Japanese patients receiving hemodialysis with anemia of CKD. Participants\u2019 treatment was switched from current erythropoiesis-stimulating agents (ESAs) to daprodustat 4 mg once daily or darbepoetin alfa 10\u201360\n                      <jats:italic toggle=\"yes\">\u03bc<\/jats:italic>\n                      g once weekly (on the basis of the prestudy ESA dose). Dose was adjusted every 4 weeks for daprodustat or every 2 weeks for darbepoetin alfa, according to a protocol-specified algorithm. The primary end point was mean hemoglobin during weeks 40\u201352 in the intent-to-treat population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 332 participants screened, 271 participants were randomized (safety evaluation: 271 participants; efficacy evaluation: 267 intent-to-treat population). The mean hemoglobin during weeks 40\u201352 were maintained within the target range in both groups (10.9 g\/dl [95% confidence interval (95% CI), 10.8 to 11.0] for daprodustat, and 10.8 g\/dl [95% CI, 10.7 to 11.0] for darbepoetin alfa). Daprodustat was noninferior to darbepoetin alfa, as the lower bound of the confidence interval for the treatment difference (0.1 g\/dl; 95% CI, \u22120.1 to 0.2 g\/dl) was greater than the noninferiority criterion of \u22121.0 g\/dl. For most participants, hemoglobin was maintained within the target range (10.0\u201312.0 g\/dl) during weeks 40\u201352 (88% daprodustat; 90% darbepoetin alfa). Geometric mean hepcidin levels decreased more at week 52 with daprodustat (\u221237%; 95% CI, \u221249 to \u221223) than with darbepoetin alfa (\u221220%; 95% CI, \u221236 to \u22121), and an increase in total iron-binding capacity was observed in the daprodustat group. Frequency of adverse events were generally similar between daprodustat and darbepoetin alfa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Oral daprodustat was noninferior to darbepoetin alfa as measured by mean hemoglobin over weeks 40\u201352 in Japanese patients receiving hemodialysis switched from ESAs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial registry name and registration number<\/jats:title>\n                    <jats:p>201754, Clinicaltrials.gov, NCT02969655.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.16011219","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T19:05:02Z","timestamp":1595963102000},"page":"1155-1165","source":"Crossref","is-referenced-by-count":117,"title":["Efficacy and Safety of Daprodustat Compared with Darbepoetin Alfa in Japanese Hemodialysis Patients with Anemia"],"prefix":"10.2215","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct02969655","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02969655","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Tadao","family":"Akizawa","sequence":"first","affiliation":[{"name":"Division of Nephrology, Showa University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaomi","family":"Nangaku","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeko","family":"Yonekawa","sequence":"additional","affiliation":[{"name":"Medicines Development, Japan Development, GlaxoSmithKline, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Okuda","sequence":"additional","affiliation":[{"name":"Medicines Development, Japan Development, GlaxoSmithKline, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Kawamatsu","sequence":"additional","affiliation":[{"name":"Clinical Operations, Japan Development, GlaxoSmithKline, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Onoue","sequence":"additional","affiliation":[{"name":"Biomedical Data Sciences, Japan Development, GlaxoSmithKline, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Endo","sequence":"additional","affiliation":[{"name":"Medicines Development, Japan Development, GlaxoSmithKline, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsutoshi","family":"Hara","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Japan Development, GlaxoSmithKline, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander R.","family":"Cobitz","sequence":"additional","affiliation":[{"name":"Medicine Delivery, GlaxoSmithKline, Collegeville, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"B1-20230813","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1681\/ASN.2011111078","article-title":"Mechanisms of anemia in CKD","volume":"23","author":"Babitt","year":"2012","journal-title":"J Am Soc Nephrol"},{"key":"B2-20230813","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/ndt\/gft443","article-title":"The iron cycle in chronic kidney disease (CKD): From genetics and experimental models to CKD 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Dis"},{"key":"B10-20230813","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1159\/000454818","article-title":"Effects of daprodustat, a novel hypoxia-inducible factor prolyl hydroxylase inhibitor on anemia management in Japanese hemodialysis subjects","volume":"45","author":"Akizawa","year":"2017","journal-title":"Am J Nephrol"},{"key":"B11-20230813","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/ckj\/sfy013","article-title":"Daprodustat for anemia: A 24-week, open-label, randomized controlled trial in participants with chronic kidney disease","volume":"12","author":"Holdstock","year":"2019","journal-title":"Clin Kidney J"},{"key":"B12-20230813","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/ckj\/sfy014","article-title":"Daprodustat for anemia: A 24-week, open-label, randomized controlled trial in participants on hemodialysis","volume":"12","author":"Meadowcroft","year":"2019","journal-title":"Clin Kidney 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