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

Not Applicable

Terminated

Conditions: All-cause Mortality
Hospitalization

Interventions: Procedure: Hemodialysis

Registration Number: NCT04095039

Lead Sponsor: Duke University

Brief 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

Detailed Description: 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)

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 793

Inclusion Criteria

Adults over 18 years of age
Undergoing 3 times weekly in-center hemodialysis and have been receiving dialysis treatment for at least 3 months
Able to provide written informed consent

Exclusion Criteria

Pregnancy
In-center Nocturnal
Calciphylaxis

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hi Arm	Hemodialysis	Patients to allow blood serum phosphate levels to rise to 6.5 mg/dl or above

Primary Outcome Measures

Name	Time	Method
Hierarchical Composite Mortality and All Cause Hospitalization	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

Secondary Outcome Measures

Name	Time	Method
Time to All-cause-mortality	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.
Hospitalization Days	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.)
Serum Albumin	Baseline (days -30 - 0)	serum albumin as markers of diet and nutrition.
Protein Catabolic Rate (PCR)	Baseline (days -30 - 0)	protein catabolic rate (PCR) as markers of diet and nutrition (g/kg/day).

Trial Locations

Locations (84): DaVita El Dorado Dialysis
🇺🇸
Long Beach, California, United States
DaVita Troup County Dialysis
🇺🇸
LaGrange, Georgia, United States
DaVita Ouachita Valley
🇺🇸
Camden, Arkansas, United States
DaVita Bloomington
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Bloomington, Minnesota, United States
DaVita Stony Island
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Chicago, Illinois, United States
DaVita Torrington
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Torrington, Connecticut, United States
DaVita Northeast Cambridge
🇺🇸
Cambridge, Massachusetts, United States
DaVita Mena
🇺🇸
Mena, Arkansas, United States
DaVita New Britain
🇺🇸
New Britain, Connecticut, United States
DaVita Thomaston Dialysis
🇺🇸
Thomaston, Georgia, United States
DaVita Phoenix Dialysis
🇺🇸
Phoenix, Arizona, United States
DaVita Hamden
🇺🇸
Hamden, Connecticut, United States
DaVita Vincennes Dialysis
🇺🇸
Vincennes, Indiana, United States
DaVita South Arkansas
🇺🇸
El Dorado, Arkansas, United States
DaVita Celebration Dialysis
🇺🇸
Kissimmee, Florida, United States
DaVita Eden Prairie
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Eden Prairie, Minnesota, United States
DaVita Pahrump
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Pahrump, Nevada, United States
DaVita Highland Park
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Highland Park, Michigan, United States
DaVita Maple Grove
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Maple Grove, Minnesota, United States
DaVita Bronx
🇺🇸
Bronx, New York, United States
Kerr Lake
🇺🇸
Louisburg, North Carolina, United States
Payson Dialysis
🇺🇸
Payson, Utah, United States
DaVita Goldsboro South Dialysis
🇺🇸
Goldsboro, North Carolina, United States
DaVita Moore
🇺🇸
Moore, Oklahoma, United States
DaVita Radnor
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Radnor, Pennsylvania, United States
DaVita Bountiful Dialysis
🇺🇸
Bountiful, Utah, United States
DaVita Fayetteville
🇺🇸
Fayetteville, Arkansas, United States
DaVita West Joliet
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Joliet, Illinois, United States
DaVita Wellington Circle
🇺🇸
Medford, Massachusetts, United States
DaVita Cottage Grove
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Cottage Grove, Minnesota, United States
DaVita Moorehead
🇺🇸
Dilworth, Minnesota, United States
DaVita Lakeville
🇺🇸
Lakeville, Minnesota, United States
DaVita Northfield
🇺🇸
Northfield, Minnesota, United States
DaVita St. Louis Park
🇺🇸
Saint Louis Park, Minnesota, United States
North Burlington Dialysis
🇺🇸
Burlington, North Carolina, United States
DaVita Orchard Park Dialysis
🇺🇸
West Seneca, New York, United States
Vance County Dialysis
🇺🇸
Henderson, North Carolina, United States
American Fork Dialysis
🇺🇸
American Fork, Utah, United States
DaVita Tahlequah
🇺🇸
Tahlequah, Oklahoma, United States
DaVita McKeesport West
🇺🇸
McKeesport, Pennsylvania, United States
Renal Center of Waterton
🇺🇸
Tyler, Texas, United States
DaVita Sandy Dialysis
🇺🇸
Sandy, Utah, United States
DaVita San Diego South
🇺🇸
San Diego, California, United States
DaVita Centennial
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Las Vegas, Nevada, United States
Durham West Dialysis
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Durham, North Carolina, United States
DaVita Minneapolis Uptown
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Minneapolis, Minnesota, United States
Durham Dialysis
🇺🇸
Durham, North Carolina, United States
Bull City Dialysis
🇺🇸
Durham, North Carolina, United States
Southpoint Dialysis
🇺🇸
Durham, North Carolina, United States
DaVita Coon Rapids
🇺🇸
Coon Rapids, Minnesota, United States
DaVita Arden Hills
🇺🇸
Arden Hills, Minnesota, United States
DaVita Burnsville
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Burnsville, Minnesota, United States
DaVita Scott County
🇺🇸
Savage, Minnesota, United States
DaVita New Ulm
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New Ulm, Minnesota, United States
DaVita Wyoming
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Wyoming, Minnesota, United States
DaVita Historical Hastings
🇺🇸
Hastings, Minnesota, United States
DaVita Fargo
🇺🇸
Fargo, North Dakota, United States
DaVita University Riverside
🇺🇸
Saint Paul, Minnesota, United States
DaVita Cass Lake
🇺🇸
Cass Lake, Minnesota, United States
DaVita East River Road
🇺🇸
Fridley, Minnesota, United States
DaVita Minnetonka
🇺🇸
Minnetonka, Minnesota, United States
DaVita Faribault
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Faribault, Minnesota, United States
DaVita Redwood Falls
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Redwood Falls, Minnesota, United States
DaVita West St. Paul
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W. Saint Paul, Minnesota, United States
DaVita St. Paul
🇺🇸
Saint Paul, Minnesota, United States
DaVita Sun Ray
🇺🇸
Saint Paul, Minnesota, United States
DaVita Glencoe
🇺🇸
Glencoe, Minnesota, United States
DaVita Richfield
🇺🇸
Richfield, Minnesota, United States
DaVita Middlesex
🇺🇸
Middletown, Connecticut, United States
DaVita Farmington Bay Dialysis
🇺🇸
Layton, Utah, United States
Provo Dialysis
🇺🇸
Provo, Utah, United States
DaVita Springdale
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Springdale, Arkansas, United States
Sandy Dialysis
🇺🇸
Taylorsville, Utah, United States
DaVita Southern Pines Dialysis
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Southern Pines, North Carolina, United States
DaVita Ensley
🇺🇸
Birmingham, Alabama, United States
DaVita Rochester
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Rochester, Minnesota, United States
DaVita Omaha West Dialysis
🇺🇸
Omaha, Nebraska, United States
DaVita Kolff
🇺🇸
Salt Lake City, Utah, United States
Burlington Dialysis
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Burlington, North Carolina, United States
DaVita Midwest Fairborn
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Fairborn, Ohio, United States
DaVita Blount Dialysis
🇺🇸
Maryville, Tennessee, United States
DaVita Reidsville Dialysis
🇺🇸
Reidsville, North Carolina, United States
DaVita Roxboro Dialysis
🇺🇸
Roxboro, North Carolina, United States
DaVita Federal Way Dialysis
🇺🇸
Federal Way, Washington, United States

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

Recruitment & Eligibility

Study & Design

Trial Locations

Instant Trial Alerts

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