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NCT04095039

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

Terminated NA Results posted Last updated 24 April 2025
What this trial tests

NA trial testing Hemodialysis in All-cause Mortality in 793 participants. Terminated before completion.

Timeline
11 March 2020
Primary endpoint
17 November 2023
17 November 2023

Quick facts

Lead sponsorDuke University
PhaseNA
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment793
Start date11 March 2020
Primary completion17 November 2023
Estimated completion17 November 2023
Sites84 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Duke University

Who can join

18 and older, any sex, with All-cause Mortality or Hospitalization. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Hierarchical Composite Mortality and All Cause Hospitalization Primary · up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months

Hierarchical composite of time to all-cause mortality and all-cause hospitalization rate (total counts per person-years of follow-up) for the individually randomized cohort

All-cause mortality
GroupValue95% CI
Lo Arm2
Hi Arm5
All-cause Hospitalizations
GroupValue95% CI
Lo Arm98
Hi Arm128
Time to All-cause-mortality Secondary · up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months

Time to all-cause-mortality from baseline for both cluster-randomized and individually randomized cohorts.

GroupValue95% CI
Lo Arm1.2± 0.72
Hi Arm1.4± 0.80
Hospitalization Days Secondary · up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months

Total days hospitalized (Data reflects participants with valid, non-missing hospitalization start and end dates.)

GroupValue95% CI
Lo Arm27.9± 29.4
Hi Arm35.4± 46.1
Serum Albumin Secondary · Baseline (days -30 - 0)

serum albumin as markers of diet and nutrition.

GroupValue95% CI
Lo Arm4.1± 0.35
Hi Arm4.1± 0.35
Protein Catabolic Rate (PCR) Secondary · Baseline (days -30 - 0)

protein catabolic rate (PCR) as markers of diet and nutrition (g/kg/day).

GroupValue95% CI
Hi Arm1.0± 0.29
Lo Arm1.1± 0.32

Sponsor's own description

HiLo will be a pragmatic, open-label, multicenter, clinical trial with individual level randomization of \~4400 patients with ESRD undergoing in-center maintenance hemodialysis at 120-150 units maintained by two dialysis organizations that care for a substantial proportion of the US dialysis population. The 1st objective of HiLo is to test the following primary and secondary hypotheses of HiLo: Primary hypothesis: Compared to the current standard approach of targeting serum phosphate levels of \<5.5 mg/dl, less stringent control of serum phosphate to target levels of ≥6.5 mg/dl will yield a reduction in the hierarchical composite outcome of time to all-cause mortality and all-cause hospitalization among patients with ESRD undergoing hemodialysis. Secondary hypothesis: The main secondary hypotheses are that less stringent control of serum phosphate will reduce risk of all-cause mortality as well as the risk of all-cause hospitalization (individually) compared to the current standard approach of strict phosphate control (superiority analysis). In addition, the trial will test the secondary hypotheses that less stringent control of serum phosphate will result in increased serum albumin and protein catabolic rate (PCR), as markers of diet and nutrition. The 2nd objective of HiLo is to conduct a second-generation pragmatic clinical trial in dialysis. In partnership with two dialysis provider organizations, demonstrate the following for a trial embedded in clinical care delivery: 1. Feasibility of obtaining informed consent using electronic devices (e-consent) 2. Use of a single IRB of record for hundreds of dialysis facilities 3. Successful implementation of a trial-driven treatment algorithm by dietitians at the participating dialysis units 4. Harmonization of data from a large for-profit dialysis provider and an academically-owned small dialysis provider 5. Effective monitoring of trial implementation using a centralized approach

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Enhancing the use of EHR systems for pragmatic embedded research: lessons from the NIH Health Care Systems Research Collaboratory.
    Richesson RL, Marsolo KS, Douthit BJ, Staman K, et al · · 2021 · cited 41× · PMID 34597383 · DOI 10.1093/jamia/ocab202
  2. Design and Rationale of HiLo: A Pragmatic, Randomized Trial of Phosphate Management for Patients Receiving Maintenance Hemodialysis.
    Edmonston DL, Isakova T, Dember LM, Brunelli S, et al · · 2021 · cited 36× · PMID 33279558 · DOI 10.1053/j.ajkd.2020.10.008
  3. State-of-the-Art Management of Hyperphosphatemia in Patients With CKD: An NKF-KDOQI Controversies Perspective.
    Scialla JJ, Kendrick J, Uribarri J, Kovesdy CP, et al · · 2021 · cited 27× · PMID 32771650 · DOI 10.1053/j.ajkd.2020.05.025
  4. 'Phos'tering a Clear Message: The Evolution of Dietary Phosphorus Management in Chronic Kidney Disease.
    Biruete A, Hill Gallant KM, Lloyd L, Meade A, et al · · 2023 · cited 17× · PMID 37343779 · DOI 10.1053/j.jrn.2023.05.004
  5. Serum phosphate and chronic kidney and cardiovascular disease: Phosphorus potential implications in general population.
    Raikou VD. · · 2021 · cited 16× · PMID 34631478 · DOI 10.5527/wjn.v10.i5.76
  6. The impact of COVID-19 on pragmatic clinical trials: lessons learned from the NIH Health Care Systems Research Collaboratory.
    O'Brien EC, Sugarman J, Weinfurt KP, Larson EB, et al · · 2022 · cited 9× · PMID 35597988 · DOI 10.1186/s13063-022-06385-8
  7. The Pathologic Actions of Phosphate in CKD.
    Fajol A, Faul C. · · 2025 · cited 3× · PMID 40241437 · DOI 10.34067/kid.0000000820
  8. Monitoring in pragmatic trials lessons from the NIH pragmatic trials collaboratory.
    Curtis LH, Morain S, O'Rourke PP, Staman K, et al · · 2025 · cited 2× · PMID 40015598 · DOI 10.1016/j.cct.2025.107866

Verify or expand the search:

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Trials by the same sponsor.

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