Key Points

The HiLo pragmatic, multicenter randomized trial compared a higher versus lower serum phosphate target in patients undergoing maintenance hemodialysis.The HiLo trial was terminated early due to insufficient enrollment and inadequate phosphate separation between groups.HiLo demonstrated the feasibility of embedding a randomized intervention in routine dialysis care and identified challenges to inform future trials.

Background

Serum phosphate targets in maintenance hemodialysis are based on observational studies. The Pragmatic Trial of Higher versus Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo) trial aimed to compare the effect of a higher versus a lower phosphate target on clinical events in patients receiving maintenance hemodialysis.

Methods

HiLo was a pragmatic, multicenter randomized trial that compared higher (≥6.5 mg/dl; “Hi”) versus lower (

Results

Between March 2020 and November 2023, 352 patients in the Hi group and 441 in the Lo group were enrolled. After a median follow-up of 1.4 years (quartiles 1–3: 0.5–2.8 years), there were 11 deaths per 100 person-years in the Hi group and 13 per 100 person-years in the Lo group. The Hi group experienced 134 hospitalizations per 100 person-years compared with 96 per 100 person-years in the Lo group. The primary hierarchical composite outcome did not differ between groups (win ratio for Hi versus Lo targets was 0.97; 95% confidence interval, 0.55 to 1.71).

Conclusions

Insufficient enrollment and inadequate phosphate separation between groups preclude inferences about the effects of phosphate targets on clinical outcomes.

Clinical Trial registry name and registration number:

ClinicalTrials.gov, NCT04095039.