HiLo: Pragmatic Trial of Higher vs Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis

Pragmatic Trial Demonstration Goals The HiLo Trial is one of the pragmatic trial demonstration projects of the NIH Health Care Systems (HCS) Research Collaboratory. These demonstration projects are intended to be large clinical trials that are conducted within the clinical care environment and evaluate interventions implemented by care providers and relying as much as possible on data obtained as part of routine clinical care. HiLo has the following demonstration project goals: 1. To implement an electronic consent process; 2. To use a single IRB of record to oversee hundreds of dialysis facilities; 3. To implement a trial-driven treatment algorithm by dietitians at the participating dialysis units 4. To harmonize across 2 different dialysis providers data elements obtained though clinical care; 5. To monitor safety without using individual adverse event reporting. HiLo will individually randomize participants using facility-level stratification to achieve balance across the two arms. Stratification will be 1:1 within each facility. Participants will be followed for up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months. Two phosphate titration protocols will be used that have the same "look and feel" as those used in practice in an effort to sustain a mean time-averaged difference in serum phosphate between the two arms of ≥1 mg/dl: 1. Low serum phosphate target that is consistent with current standard of care: The goal is to titrate and maintain serum phosphate to \<5.5 mg/dl. 2. Higher serum phosphate target that is the intervention strategy: The goal is to titrate and maintain serum phosphate to ≥6.5 mg/dl by setting a serum phosphate threshold \>7.0 mg/dl when binders will be initiated, as has been done previously. A mean serum phosphate of 4.8-5.2 is anticipated in the low arm and 6.5-6.8 in the high arm, as observed in two pilot clinical trials.Since serum phosphate is 4-7 mg/dl in most patients with ESRD, ≥1 mg/dl difference equates with a ≥33% difference within the modifiable range of time-averaged phosphate exposure. Specific binder choices will be relegated to the discretion of local providers based on local practice. Planned Enrollment and randomization Enrollment of the first subject - 03/13/2020 (Actual) 25% of planned enrollment recruited - 06/30/2022 (Anticipated) 50% of planned enrollment recruited - 10/30/2022 (Anticipated) 75% of planned enrollment recruited - 03/31/2023 (Anticipated) 100% of planned enrollment recruited - 09/30/2023 (Anticipated) 6.4. Completion of primary endpoint data analyses - 11/30/2024 (Anticipated) 6.5. Reporting of results in ClinicalTrials.gov - 1/31/2025 (Anticipated)