The ASCEND-ND trial: study design and participant characteristics

Vlado Perkovic, Allison Blackorby, Borut Cizman, Kevin Carroll, Alexander R Cobitz, Rich Davies, Tara L DiMino, Vivekanand Jha, Kirsten L Johansen, Renato D Lopes, Lata Kler, Iain C Macdougall, John J V McMurray, Amy M Meadowcroft, Gregorio T Obrador, Scott Solomon, Lin Taft, Christoph Wanner, Sushrut S Waikar, David C Wheeler, Andrzej Wiecek, Ajay K Singh, Vlado Perkovic, Allison Blackorby, Borut Cizman, Kevin Carroll, Alexander R Cobitz, Rich Davies, Tara L DiMino, Vivekanand Jha, Kirsten L Johansen, Renato D Lopes, Lata Kler, Iain C Macdougall, John J V McMurray, Amy M Meadowcroft, Gregorio T Obrador, Scott Solomon, Lin Taft, Christoph Wanner, Sushrut S Waikar, David C Wheeler, Andrzej Wiecek, Ajay K Singh

Abstract

Background: Anaemia is common in chronic kidney disease (CKD) and assessment of the risks and benefits of new therapies is important.

Methods: The Anaemia Study in CKD: Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Non-Dialysis (ASCEND-ND) trial includes adult patients with CKD Stages 3-5, not using erythropoiesis-stimulating agents (ESAs) with screening haemoglobin (Hb) 8-10 g/dL or receiving ESAs with screening Hb of 8-12 g/dL. Participants were randomized to daprodustat or darbepoetin alfa (1:1) in an open-label trial (steering committee- and sponsor-blinded), with blinded endpoint assessment. The co-primary endpoints are mean change in Hb between baseline and evaluation period (average over Weeks 28-52) and time to first adjudicated major adverse cardiovascular (CV) event. Baseline characteristics were compared with those of participants in similar anaemia trials.

Results: Overall, 3872 patients were randomized from 39 countries (median age 67 years, 56% female, 56% White, 27% Asian and 10% Black). The median baseline Hb was 9.9 g/dL, blood pressure was 135/74 mmHg and estimated glomerular filtration rate was 18 mL/min/1.73 m2. Among randomized patients, 53% were ESA non-users, 57% had diabetes and 37% had a history of CV disease. At baseline, 61% of participants were using renin-angiotensin system blockers, 55% were taking statins and 49% were taking oral iron. Baseline demographics were similar to those in other large non-dialysis anaemia trials.

Conclusion: ASCEND-ND will define the efficacy and safety of daprodustat compared with darbepoetin alfa in the treatment of patients with anaemia associated with CKD not on dialysis.

Trial registration: ClinicalTrials.gov NCT02876835.

Keywords: anaemia; baseline data; chronic kidney disease; daprodustat, darbepoetin alfa.

© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.

Figures

Graphical Abstract
Graphical Abstract
FIGURE 1:
FIGURE 1:
ASCEND-ND study design. Serum and plasma samples are collected at baseline, Week 28 and Week 52 for future analysis of biomarkers of CV risk and iron metabolism. EOS, end of study; Hb, haemoglobin; MACE, major adverse cardiovascular event; QD, once daily; SC, subcutaneous; TSAT, transferrin saturation.
FIGURE 2:
FIGURE 2:
ASCEND-ND country-level participant distribution. APAC; Asia Pacific; EMEA: Europe, Middle East and Africa.

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