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Abstract: FR-OR27

Reduction of Calciphylaxis-Related Infections with Hexasodium Fytate Treatment in a Randomized, Double-Blind, Phase 3, Placebo-Controlled Trial

Session Information

Category: Dialysis

  • 801 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Sinha, Smeeta, Northern Care Alliance NHS Foundation Trust, Salford, United Kingdom
  • Nigwekar, Sagar U., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Gould, Lisa, South Shore Hospital, Weymouth, Massachusetts, United States
  • Serena, Thomas E., SerenaGroup Research Foundation, Cambridge, Massachusetts, United States
  • Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Aronoff, George R., DaVita Inc, Denver, Colorado, United States
  • Chatoth, Dinesh K., Fresenius Medical Care Holdings Inc, Waltham, Massachusetts, United States
  • Hymes, Jeffrey L., Fresenius Medical Care Holdings Inc, Waltham, Massachusetts, United States
  • Alperovich Lehrer, Gabriela, Vifor Pharma Management AG, Glattbrugg, Zurich, Switzerland
  • Keller, Laurence H., Clinical Development Consultant, Ann Arbor, Michigan, United States
  • Gold, Alex, Clinical Development Consultant, Incline Village, Nevada, United States
  • Szecsödy, Peter, Vifor Pharma Management AG, Glattbrugg, Zurich, Switzerland
  • Radewonuk, Jana, CSL Behring LLC, King of Prussia, Pennsylvania, United States
  • Perelló, Joan, Vifor Pharma Management AG, Glattbrugg, Switzerland
  • Chertow, Glenn M., Stanford University School of Medicine, Stanford, California, United States

Group or Team Name

  • CALCIPHYX Study Investigators.
Background

CALCIPHYX was an international, phase 3, randomized, double-blind, placebo-controlled clinical trial that investigated hexasodium fytate (SNF472), an inhibitor of vascular calcification, for the treatment of calciphylaxis. Infection of calciphylaxis skin lesions is a serious complication and effective strategies to reduce the rate of calciphylaxis-related infection are lacking. In this post-hoc analysis, we compare rates of calciphylaxis-related infections between groups as randomized through Week 12.

Methods

Adults with an ulcerated calciphylaxis lesion and pain visual analog scale score ≥50/100 received double-blind hexasodium fytate 7 mg/kg or placebo intravenously during maintenance hemodialysis to Week 12 and open label hexasodium fytate to Week 24 with an end of study (EOS) visit at Week 28. Exploratory post-hoc analyses of calciphylaxis-related infection (adverse events in the Infections and Infestations system organ class) included time to first event (Kaplan-Meier, Greenwood variance with hazard ratio and confidence interval [CI] by bootstrapping Cox proportional regression and Exact Wilcoxon p-value) and rate ratios (negative binomial regression). P-values were nominal.

Results

Any calciphylaxis-related infection was reported for 1/37 patients (1 event total) in the hexasodium fytate group and 7/34 patients (10 events total) in the placebo group (Figure). The hazard ratio for hexasodium fytate vs placebo at Weeks 12 and 24 was 0.11 (95% CI: 0.00-0.64; p=0.026). Exposure-adjusted rate ratios for hexasodium fytate vs placebo were: Week 12, 0.086 (95% CI: 0.021-0.346; p<0.001); Week 24, 0.061 (95% CI: 0.015-0.250; p<0.001); and EOS, 0.057 (95% CI: 0.014-0.238; p<0.001).

Conclusion

In this exploratory analysis, hexasodium fytate treatment during hemodialysis reduced the incidence of first and multiple calciphylaxis-related infections.

Figure. Time to first calciphylaxis-related infection

Funding

  • Commercial Support – Sanifit, a CSL Vifor company