Trial Summary

Study question and significance: Serum phosphate targets in maintenance hemodialysis are based on observational studies. It is unknown whether a higher or lower target for phosphate control offers the best balance of benefits and risks.

Design and setting: Multicenter, pragmatic clinical trial comparing the effects of a higher vs lower phosphate target on all-cause mortality and all-cause hospitalization in patients receiving maintenance hemodialysis within a large dialysis organization between March 2020 and November 2023. The study began as a cluster randomized trial with randomization at the dialysis facility level. Because of an observed imbalance in baseline serum phosphate between the study groups approximately 2 years into the study, the study team transitioned to patient-level randomization.

Intervention and methods: Patients in the low phosphate target group received the standard clinical approaches to phosphate management. For patients in the high phosphate target group, clinicians and dietitians withdrew phosphate binders and relaxed dietary restrictions if the phosphate level remained below target. The primary outcome was a composite outcome of all-cause mortality and all-cause hospitalization.

Findings: After enrollment of 792 patients, the study was stopped early due to insufficient enrollment and inadequate phosphate separation between the study arms. As a result, the study team was unable to detect a difference in the primary outcome and to make inferences about secondary outcomes.

Conclusions and relevance: The trial’s design had several pragmatic features that point the way for future trials. The trial used no onsite research staff, instead engaging sites' clinical staff to deliver the intervention as part of routine care. The study team monitored monthly laboratory data remotely and provided real-time feedback to the sites. All laboratory and outcome data were collected in the context of clinical care. Disruptions from the COVID-19 pandemic, complications related to the trial's original cluster randomized design, and other challenges also offer lessons for future studies.

NIH Project Information