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

Sponsor

Duke University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04095039

Collaborator

Northwestern University (Other), University of Pennsylvania (Other), Davita Clinical Research (Industry), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), American Association of Kidney Patients (Other)

4,400

Enrollment

Locations

Arms

61.6

Anticipated Duration (Months)

122.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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:

Feasibility of obtaining informed consent using electronic devices (e-consent)
Use of a single IRB of record for hundreds of dialysis facilities
Successful implementation of a trial-driven treatment algorithm by dietitians at the participating dialysis units
Harmonization of data from a large for-profit dialysis provider and an academically-owned small dialysis provider
Effective monitoring of trial implementation using a centralized approach

Condition or Disease	Intervention/Treatment	Phase
Mortality	Procedure: Hemodialysis	N/A

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:

To implement an electronic consent process;
To use of a single IRB of record to oversee hundreds of dialysis facilities;
To implement a trial-driven treatment algorithm by dietitians at the participating dialysis units
To harmonize across 2 different dialysis providers data elements obtained though clinical care;
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:

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.
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)

Study Design

Study Type:

Interventional

Anticipated Enrollment :

4400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 13, 2020

Anticipated Primary Completion Date :

Apr 30, 2025

Anticipated Study Completion Date :

Apr 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hi Arm Patients to allow blood serum phosphate levels to rise to 6.5 mg/dl or above	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
No Intervention: Lo Arm Patients to titrate blood serum phosphate levels to the standard <5.5mg/dl

Arm

Intervention/Treatment

Experimental: Hi Arm

Patients to allow blood serum phosphate levels to rise to 6.5 mg/dl or above

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

No Intervention: Lo Arm

Patients to titrate blood serum phosphate levels to the standard <5.5mg/dl

Outcome Measures

Primary Outcome Measures

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).

Secondary Outcome Measures

Time to all-cause mortality [up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months]
Time to all-cause mortality
all-cause hospitalization rate [up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months]
all-cause hospitalization rate, expressed as total counts per person-years of follow-up.
Total Inpatient Hospital Days [up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months]
total inpatient hospital days per person-years of follow-up;
serum albumin [up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months]
serum albumin as markers of diet and nutrition.
protein catabolic rate (PCR) [up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months]
protein catabolic rate (PCR) as markers of diet and nutrition.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	DaVita Ensley	Birmingham	Alabama	United States	35218
2	DaVita Phoenix Dialysis	Phoenix	Arizona	United States	85004
3	DaVita El Dorado Dialysis	Long Beach	California	United States	90806
4	DaVita San Diego South	San Diego	California	United States	27560
5	DaVita Celebration Dialysis	Kissimmee	Florida	United States	34747
6	DaVita Troup County Dialysis	LaGrange	Georgia	United States	30240
7	DaVita Thomaston Dialysis	Thomaston	Georgia	United States	30286
8	DaVita Stony Island	Chicago	Illinois	United States	60617
9	DaVita West Joliet	Joliet	Illinois	United States	60435
10	DaVita Vincennes Dialysis	Vincennes	Indiana	United States	47591
11	DaVita Omaha West Dialysis	Omaha	Nebraska	United States	68154
12	DaVita Orchard Park Dialysis	West Seneca	New York	United States	14127
13	Burlington Dialysis	Burlington	North Carolina	United States	27215
14	North Burlington Dialysis	Burlington	North Carolina	United States	27217-2928
15	Durham Dialysis	Durham	North Carolina	United States	27701
16	Bull City Dialysis	Durham	North Carolina	United States	27705
17	Durham West Dialysis	Durham	North Carolina	United States	27705
18	Southpoint Dialysis	Durham	North Carolina	United States	27713
19	DaVita Goldsboro South Dialysis	Goldsboro	North Carolina	United States	27534
20	Vance County Dialysis	Henderson	North Carolina	United States	27536
21	Kerr Lake	Louisburg	North Carolina	United States	27549
22	DaVita Reidsville Dialysis	Reidsville	North Carolina	United States	27320
23	DaVita Roxboro Dialysis	Roxboro	North Carolina	United States	27573
24	DaVita Southern Pines Dialysis	Southern Pines	North Carolina	United States	28387
25	DaVita Midwest Fairborn	Fairborn	Ohio	United States	45324
26	DaVita Radnor	Radnor	Pennsylvania	United States	19406
27	DaVita Blount Dialysis	Maryville	Tennessee	United States	37804
28	American Fork Dialysis	American Fork	Utah	United States	84003
29	Lakeside Dialysis	Bountiful	Utah	United States	84010
30	Farmington Bay Dialysis	Layton	Utah	United States	84041
31	Payson Dialysis	Payson	Utah	United States	84651
32	Provo Dialysis	Provo	Utah	United States	84604
33	Kolff	Salt Lake City	Utah	United States	84108
34	South Valley Dialysis	Sandy	Utah	United States	84070
35	West Valley Dialysis	Taylorsville	Utah	United States	84129
36	DaVita Federal Way Dialysis	Federal Way	Washington	United States	98003

Sponsors and Collaborators

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

Investigators

Principal Investigator: Myles Wolf, MD, MMSc, Duke Nephrology

Study Documents (Full-Text)

Study Protocol - Sep 24, 2021

More Information

Publications

None provided.

Responsible Party:

Duke University

ClinicalTrials.gov Identifier:

NCT04095039

Other Study ID Numbers:

Pro00100325
5UH3DK118748-03

First Posted:

Sep 19, 2019

Last Update Posted:

May 26, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Duke University

All-cause hopitalization

Study Results

No Results Posted as of May 26, 2022