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

Summary

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

Conditions

• All-cause Mortality
• Hospitalization

Interventions

PROCEDURE

Hemodialysis

Patients in both arms will undergo hemodialysis to remove phosphate from the blood; however, patients in the Hi Arm will only be titrated down to no lower than 6.5mg/dl

Sponsors & Collaborators

• Northwestern University

  collaborator OTHER

• University of Pennsylvania

  collaborator OTHER

• Davita Clinical Research

  collaborator INDUSTRY

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• American Association of Kidney Patients

  collaborator OTHER

• Duke University

  lead OTHER

Principal Investigators

• Myles Wolf, MD, MMSc · Duke Nephrology

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-03-11

Primary Completion

2023-11-17

Completion

2023-11-17

Countries

• United States

Study Locations