ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-OR66

ASCEND Program: Efficacy and Safety from ASCEND-D and -ND and Overall MACE Finding

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Singh, Ajay K., Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
  • Carroll, Kevin, KJC Statistics Limited, Stockport, United Kingdom
  • Perkovic, Vlado, UNSW Sydney, Newtown, New South Wales, Australia
  • Solomon, Scott D., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Jha, Vivekanand, The George Institute for Global Health India, New Delhi, Delhi, India
  • Johansen, Kirsten L., Hennepin Healthcare, Minneapolis, Minnesota, United States
  • Lopes, Renato D., Duke University, Durham, North Carolina, United States
  • Macdougall, Iain C., King's College Hospital, London, London, United Kingdom
  • Obrador, Gregorio T., Universidad Panamericana, Ciudad de Mexico, Ciudad de México, Mexico
  • Waikar, Sushrut S., Boston University, Boston, Massachusetts, United States
  • Wanner, Christoph, University Hospital, Wuerzburg, Germany
  • Wheeler, David C., University College London, London, London, United Kingdom
  • Wiecek, Andrzej, Medical University of Silesia, Katowice, Poland
  • Blackorby, Allison, GlaxoSmithKline, Durham, North Carolina, United States
  • Cizman, Borut, GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Cobitz, Alexander Ralph, GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Davies, Rich, GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Dimino, Tara L., GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Dole, Jo Forsythe, GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Kler, Lata, GlaxoSmithKline, Middlesex, United Kingdom
  • Meadowcroft, Amy M., GlaxoSmithKilne, Raleigh, North Carolina, United States
  • Taft, Lin, GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Zhu, Xinyi, GlaxoSmithKline, Stevenage, United Kingdom
  • McMurray, John, University of Glasgow, Glasgow, Glasgow, United Kingdom

Group or Team Name

  • On behalf of the ASCEND-D authors
Background

The Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis via a novel prolyl hydroxylase inhibitor Daprodustat (ASCEND) phase 3 program investigated efficacy and safety of daprodustat.

Methods

The program included 2 event-driven, cardiovascular outcomes trials (CVOTs) in non-dialysis (ASCEND-ND) and dialysis (ASCEND-D) patients comparing daprodustat with conventional ESAs. Non-inferiority (NI) co-primary endpoints included mean change in hemoglobin (Hb) between baseline and evaluation period (avg over weeks 28–52; NI margin: -0.75 g/dL) and time to first adjudicated major adverse CV event (MACE; NI margin: 1.25). Principal secondary endpoints, adjusted for multiplicity, included superiority assessments of MACE, MACE + thromboembolic events, MACE + hospitalization for heart failure and average monthly intravenous iron dose up to week 52 in ASCEND-D and time to progression of CKD in ASCEND-ND. Three smaller trials also reported adjudicated MACE but were not designed for formal MACE evaluation.

Results

8169 patients were randomized across the 5 trials, with ~14,200 person-years (PY) of follow-up in CVOTs. The co-primary NI Hb objective was met in both CVOTs (adjusted mean treatment difference [95%CI]: ASCEND-D 0.18 [0.12-0.24] g/dL, ASCEND-ND 0.08 [0.03-0.13] g/dL). The co-primary NI MACE endpoint was also met (hazard ratio [95%CI]: ASCEND-D 0.93 [0.81-1.07], ASCEND-ND 1.03 [0.89-1.19]). No principal secondary endpoints met superiority. CVOT rates of treatment emergent adverse events were similar between daprodustat and ESA groups. Figure shows program-level first adjudicated MACE rates per 100 PY (intent-to-treat); MACE rates for ASCEND-NHQ (N=614) were 4.9% for daprodustat and 6.2% for placebo).

Conclusion

CVOTs demonstrated daprodustat was non-inferior to ESA for Hb efficacy and MACE and was well-tolerated. CV safety was generally consistent across treatment groups in the other studies.