Safety and Efficacy of Vadadustat Versus Darbepoetin Alfa for Chronic Kidney Disease–Related Anemia in Patients Receiving Dialysis by Baseline Erythropoiesis‐Stimulating Agent Dose
Bibliographic record
Abstract
ABSTRACT Introduction Erythropoiesis‐stimulating agents (ESAs) and iron supplementation are standard treatments for chronic kidney disease (CKD)–related anemia. Targeting higher hemoglobin values in CKD increases cardiovascular risk. Whether the increased risk is from higher ESA doses or higher hemoglobin levels is uncertain, but alternative therapies are sought for patients requiring high ESA doses. Phase 3 INNO 2 VATE trials in patients with dialysis‐dependent CKD (DD‐CKD) demonstrated vadadustat's noninferiority compared with darbepoetin alfa. To determine vadadustat's potential to treat anemia, including in patients requiring high ESA doses, its safety and efficacy were compared with those of darbepoetin alfa across prespecified baseline ESA dose subgroups in the prevalent DD‐CKD INNO 2 VATE trial. Methods We compared the safety and efficacy of vadadustat versus darbepoetin alfa across prespecified baseline ESA dose subgroups (low [≤ 90 U/kg/week], intermediate [> 90 and < 300 U/kg/week], or high [≥ 300 U/kg/week]) in the INNO 2 VATE prevalent trial. The primary safety endpoint was time to first adjudicated major adverse cardiovascular event (MACE). Primary and secondary efficacy endpoints were mean hemoglobin level change from baseline at weeks 24–36 and weeks 40–52, respectively. Findings Compared with darbepoetin alfa, first MACE hazard ratios for vadadustat were 0.99 (95% CI, 0.81–1.23), 0.93 (95% CI, 0.74–1.18), and 0.62 (95% CI, 0.34–1.14) for low, intermediate, and high baseline ESA dose subgroups, respectively (interaction p = 0.92). Vadadustat was noninferior to darbepoetin alfa in hemoglobin change from baseline to primary evaluation period, with mean differences (vadadustat–darbepoetin alfa) of −0.10 g/dL (95% CI, −0.19 to −0.02), −0.20 g/dL (95% CI, −0.30 to −0.09), and −0.39 g/dL (95% CI, −0.67 to −0.11) for low, intermediate, and high ESA dose subgroups, respectively. Discussion Comparing safety and efficacy by baseline ESA dose among patients with CKD on maintenance dialysis, vadadustat was noninferior to darbepoetin alfa for all ESA dose subgroups, including patients with high baseline ESA requirements.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".