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

Mortality Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04095039
• Other study ID #: Pro00100325
• Secondary ID: 5UH3DK118748-03
• Status: Terminated
• Phase: N/A
• Start date: March 13, 2020
• Est. completion date: November 17, 2023

Study information

• Verified date: July 2023
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 of 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 information / eligibility

• Status: Terminated
• Enrollment: 812
• Est. completion date: November 17, 2023
• Est. primary completion date: November 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Mortality

Intervention

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

Locations

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

Sponsors (6)

Lead Sponsor	Collaborator
Duke University	American Association of Kidney Patients, Davita Clinical Research, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Northwestern University, University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hierarchical Composite Mortality and all cause hospitalization	Hierarchical composite of time to all-cause mortality and all-cause hospitalization rate (total counts per person-years of follow-up).	up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months
Secondary	Time to all-cause mortality	Time to all-cause mortality	up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months
Secondary	all-cause hospitalization rate	all-cause hospitalization rate, expressed as total counts per person-years of follow-up.	up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months
Secondary	Total Inpatient Hospital Days	total inpatient hospital days per person-years of follow-up;	up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months
Secondary	serum albumin	serum albumin as markers of diet and nutrition.	up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months
Secondary	protein catabolic rate (PCR)	protein catabolic rate (PCR) as markers of diet and nutrition.	up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months