Assessment of Thromboembolic Events with Vadadustat vs. Darbepoetin Alfa for Treatment of Anemia in Patients with Non-Dialysis-Dependent CKD
Bibliographic record
Abstract
Background: Vadadustat (VADA) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor being investigated for treatment of anemia due to chronic kidney disease (CKD). Two recently completed global phase 3, open-label, randomized (1:1), sponsor-blind, noninferiority trials (PRO2TECT) compared the safety and efficacy of VADA with that of darbepoetin alfa (DA) in adult patients with non-dialysis-dependent (NDD) CKD. One of the studies (NCT02648347) was in 1751 patients previously untreated with an erythropoiesis-stimulating agent (ESA). The other study (NCT02680574) was in 1725 ESA-treated patients. The primary safety endpoint of the PRO2TECT trials was time to first major adverse cardiovascular event (MACE; a composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke), prespecified as a pooled event-driven analysis of both trials. As previously reported, the hazard ratio (HR; VADA:DA) for MACE was 1.17 (95% confidence interval [CI], 1.01-1.36), which did not meet the prespecified noninferiority margin of 1.25. Methods: Here we describe the prespecified pooled analysis of the secondary safety endpoints of time to first thromboembolic event, including (1) any thromboembolic event (a composite of events of vascular access thrombosis, arterial thrombosis, deep venous thrombosis [DVT], and pulmonary embolism [PE]), (2) arterial thrombosis, DVT, or PE, and (3) venous thromboembolic events (DVT or PE). Results: A total of 1739 patients received VADA and 1732 received DA in these two studies. A first thromboembolic event occurred in 33 patients (1.9%) in the VADA group and 38 (2.2%) in the DA group (HR [95% CI]: 0.88 [0.554-1.408]; P value of Gray's test=0.569). For arterial thrombosis, DVT, or PE, there were 21 (1.2%) and 25 (1.4%) patients with events, respectively (HR [95% CI]: 0.86 [0.480-1.544]; P=0.569), and for venous thromboembolic events, there were 18 (1.0%) and 23 (1.3%), respectively (HR [95% CI]: 0.80 [0.430-1.485]; P=0.445). Vascular-access thrombosis was reported as <1.0 event/100 patient years in both the VADA and DA groups. Conclusions: In the phase 3 PRO2TECT trial in patients with anemia and NDD-CKD, the rate of thromboembolic events was similar between the VADA and DA groups. Funding: Commercial Support - Akebia Therapeutics, Inc., and Otsuka Pharmaceuticals Development and Commercialization, Inc.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.011 | 0.011 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.004 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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".