Abstract: SA-OR53
Hemoglobin Stability in the ASCEND-TD Trial
Session Information
- Hemodialysis Care: Cardiovascular and Patient-Reported Outcomes
November 04, 2023 | Location: Room 120, Pennsylvania Convention Center
Abstract Time: 05:15 PM - 05:24 PM
Category: Dialysis
- 801 Dialysis: Hemodialysis and Frequent Dialysis
Authors
- Acharya, Anjali, Jacobi Medical Center, Bronx, New York, United States
- Rastogi, Anjay, University of California Los Angeles, Los Angeles, California, United States
- Jha, Vivekanand, George Institute for Global Health, New Delhi, India
- Singh, Ajay K., Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
- Meadowcroft, Amy M., GSK, Collegeville, Pennsylvania, United States
- Bhatt, Purav Rahulkumar, GSK, Collegeville, Pennsylvania, United States
- Jones-Leone, Angela Renne, GSK, Collegeville, Pennsylvania, United States
- Shannon, Jennifer, GSK, Collegeville, Pennsylvania, United States
Background
Daprodustat (Dapro), a hypoxia-inducible factor–prolyl hydroxylase inhibitor (HIF-PHI), has been investigated as a treatment for anemia of chronic kidney disease (CKD) in the ASCEND program. Maintaining hemoglobin (Hb) levels in the target range per clinical guidelines for patients (pts) with CKD is complex. Primary efficacy results for dapro administered three times weekly (TIW) are reported (Coyne DW. CJASN 2022). Here we examine additional Hb stability data of Dapro dosed TIW.
Methods
ASCEND-TD (NCT03400033) was a randomized, double-blind, double-dummy, active comparator study evaluating the efficacy and safety of Dapro dosed over 52 weeks compared with epoetin alfa (EPO) in pts receiving hemodialysis. Various Hb stability measures were assessed in a pre-specified manner. Responders were defined as pts with mean Hb within the Hb analysis range (10–11.5 g/dL) during the evaluation period (EP, Weeks 28–52).
Results
322/407 (79%) pts had evaluable Hb during the EP. The difference in response rate (dapro-EPO) was 0.1645 (95% CI [0.06, 0.27]) and demonstrated nominal superiority. Median time Hb was in the analysis range (% [interquartile range]) was higher in pts administered Dapro compared with pts administered EPO (70.83 [50.98; 91.07] and 61.76 [29.69; 85.19], respectively). The Hodges-Lehmann estimate of the median treatment difference (dapro-EPO) of 11.18% met non-inferiority. Dapro TIW was also nominally superior to EPO for percentage of time Hb was within the analysis range according to the van Elteren’s test stratified by region (one-sided P=0.0034; Table). The proportion of pts with evaluable Hb <7.5 g/dL and ≥12 g/dL during the EP and the proportion of time Hb ≥12 g/dL during the EP was lower in pts administered Dapro compared with pts administered EPO.
Conclusion
In ASCEND-TD, Dapro TIW demonstrated a potential benefit in maintaining stable Hb compared with EPO. Further analysis is required to understand this effect and to provide conclusive evidence of better Hb stability for Dapro compared with EPO.
| Table. Analysis of % time Hb within the analysis range during the EP using evaluable Hb values | ||
| Daprodustat (N=270) | EPO (N=137) | |
| n† (%) | 215 (80) | 107 (78) |
| Median (%) time in range (10–11.5 g/dL) | 70.83 | 61.76 |
| Hodges–Lehmann estimate of treatment difference (daprodustat−EPO) (%) | 11.18 | |
| Hodges–Lehmann two-sided asymptotic 95% CI (%) | (2.83, 19.56) | |
| One-sided P-value‡ | 0.0034 | |
| †Participants who have at least two post-randomization evaluable Hb values on different days, where at least one evaluable Hb value is contained within the EP and another evaluable Hb value occurs within the range of the Week 16 visit through to the Week 52 visit, inclusive. ‡Treatment group comparisons are based on van Elteren's test stratified by region. CI, confidence interval; EP, evaluation period; EPO, epoetin alfa; Hb, hemoglobin. | ||
Funding
- Commercial Support – The study and this analysis were funded by GSK.