Trial Design of FRONTIER: Ferric Citrate for the Prevention of Renal Failure in Adults with Advanced CKD
Bibliographic record
Abstract
Background: There are no approved therapies to delay progression to RRT or improve survival specifically in patients with advanced CKD regardless of etiology. A pilot, open-label randomized trial in 200 patients with estimated GFR < 20 ml/min/1.73m2 demonstrated statistically significant reduction in the risk of the composite endpoint of death, dialysis or transplantation in patients randomized to fixed dose ferric citrate coordination complex (FCCC) as compared to standard of care (SOC). The current trial is designed to overcome the limitations of this open-label RCT by using a pragmatic, placebo-controlled, randomized trial design. Methods: FRONTIER will enroll 1000 patients with estimated GFR < 20 ml/min/1.73m2 who will be randomized 1:1 to either fixed dose FCCC (2 tablets/meal) or matching placebo. Enrollment will not be based on serum concentrations reflecting iron sufficiency or phosphate. Subjects will be followed for 18 months using a pragmatic schedule based solely on SOC visits. No additional trial specific visits or laboratory tests will be required. The primary objective is to determine the effect of FCCC on the time to a composite endpoint of initiation of maintenance dialysis or all-cause mortality compared to placebo. The secondary objective is to evaluate the impact of FCCC on all-cause hospitalization and the individual components of the primary endpoint. Results: FRONTIER is a collaboration between Industry (Akebia Therapeutics is providing study medication and funding), community nephrologists (planned for 42 sites in the US) and academia. An executive steering committee has designed the clinical trial protocol and US Renal Care, Inc will be acting as the Sponsor-Investigator. Conclusions: Based on supportive pilot data, FRONTIER will utilize a novel trial design incorporating a pragmatic approach while maintaining a randomized, placebo-control arm and generating real-world evidence to determine the effects of FCCC on clinically meaningful patient outcomes (time to dialysis or all-cause mortality). Funding: Commercial Support - Akebia Therapeutics
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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 | 0.014 | 0.016 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.010 | 0.001 |
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".