Kidney Week

Abstract: TH-PO1187

Ferric Citrate for the Prevention of Renal Failure in Adults with Advanced CKD: The FRONTIER Trial

Session Information

• Late-Breaking Science Posters
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Block, Geoffrey A., US Renal Care, Plano, Texas, United States

Geoffrey A. Block, MD, FASN

• Burke, Steven K., Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Steven K. Burke, MD

• Block, Martha, US Renal Care, Plano, Texas, United States

Martha Block, RN

• Brillhart, Stephanie, US Renal Care, Plano, Texas, United States

Stephanie Brillhart, MS

• Leppink, Amanda, US Renal Care, Plano, Texas, United States

Amanda Leppink

• Smits, Gerard John, CSC, Inc., Santa Barbara, California, United States

Gerard John Smits, PhD

• Mizani, Mohammad R., South Texas Renal Care Group, San Antonio, Texas, United States

Mohammad R. Mizani, MD, FASN

• Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States

Pablo E. Pergola, MD, PhD

• Newby, F. David, Nephrology and Hypertension Specialists, PC, Dalton, Georgia, United States

F. David Newby, MD, PhD

• Broumand, Varshasb, South Texas Renal Care Group, San Antonio, Texas, United States

Varshasb Broumand, MD, FASN

• Foote, Bryce Stephen, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Bryce Stephen Foote, PharmD

• Dittrich, Mary O., US Renal Care, Plano, Texas, United States

Mary O. Dittrich, MD

Background

In a prior study of patients (pts) with advanced CKD, Ferric Citrate (FC) significantly reduced time to a composite endpoint of death, dialysis or kidney transplant. Important study design limitations constrain the interpretation of these findings.

Methods

In this 9-month, randomized, double-blind, placebo-controlled clinical trial, pts with eGFR ≤20 ml/min/1.73m² were randomized 1:1 to receive fixed dose (2 tablets/meal) FC or matching placebo. The primary endpoint was time to a composite endpoint of initiation of maintenance dialysis or all-cause mortality. Secondary endpoints were time to first hospitalization and individual components of the primary endpoint. Analysis used ITT with ANCOVA adjusting for age, baseline eGFR, and history of diabetes, ASCVD and CHF.

Results

289 pts were randomized to FC (n=144) or placebo (n=145). The treatment arms were well balanced with no statistical differences in pt characteristics. We observed a statistically non-significant 27% reduction in risk of the primary composite endpoint, (Fig. 1, p=0.12). Individual components of the primary endpoint are shown in Fig. 1. 24% of pts randomized to FC experienced ≥1 serious adverse events vs 32% of pts given placebo. FC was associated with a statistically non-significant reduction in mean hospitalizations (p=0.46), mean hospital days (p=0.41) and time to first hospitalization (p=0.22) (Fig. 2). Similarly, there was a statistically non-significant reduction in time to first ESA use (p=0.79) and time to first IV iron use (p=0.07).

Conclusion

In pts with advanced CKD, fixed dose FC resulted in clinically meaningful, though statistically non-significant, reductions in time to the composite endpoint of death or dialysis, hospitalization, ESA use and IV iron use. The sample size of the trial likely reduced the ability to demonstrate statistically significant results. These findings strongly suggest that re-purposing FC for prevention of kidney failure in pts with advanced CKD may meaningfully improve outcomes.

Funding

• Commercial Support – Akebia Therapeutics Inc