Study Stopped
Futility of enrollment and futility of separation between study arms
HiLo: Pragmatic Trial of Higher vs Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis
2 other identifiers
interventional
793
1 country
84
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Mar 2020
Longer than P75 for not_applicable
84 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 10, 2019
CompletedFirst Posted
Study publicly available on registry
September 19, 2019
CompletedStudy Start
First participant enrolled
March 11, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 17, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
November 17, 2023
CompletedResults Posted
Study results publicly available
January 8, 2025
CompletedApril 24, 2025
July 1, 2023
3.7 years
September 10, 2019
November 15, 2024
April 17, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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) for the individually randomized cohort
up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months
Secondary Outcomes (4)
Time to All-cause-mortality
up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months
Hospitalization Days
up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months
Serum Albumin
Baseline (days -30 - 0)
Protein Catabolic Rate (PCR)
Baseline (days -30 - 0)
Study Arms (2)
Hi Arm
EXPERIMENTALPatients to allow blood serum phosphate levels to rise to 6.5 mg/dl or above
Lo Arm
NO INTERVENTIONPatients to titrate blood serum phosphate levels to the standard \<5.5mg/dl
Interventions
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
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- Pregnancy
- In-center Nocturnal
- Calciphylaxis
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Duke Universitylead
- Northwestern Universitycollaborator
- University of Pennsylvaniacollaborator
- Davita Clinical Researchcollaborator
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)collaborator
- American Association of Kidney Patientscollaborator
Study Sites (84)
DaVita Ensley
Birmingham, Alabama, 35218, United States
DaVita Phoenix Dialysis
Phoenix, Arizona, 85004, United States
DaVita Ouachita Valley
Camden, Arkansas, 71701, United States
DaVita South Arkansas
El Dorado, Arkansas, 71730, United States
DaVita Fayetteville
Fayetteville, Arkansas, 72703, United States
DaVita Mena
Mena, Arkansas, 71953, United States
DaVita Springdale
Springdale, Arkansas, 71953, United States
DaVita El Dorado Dialysis
Long Beach, California, 90806, United States
DaVita San Diego South
San Diego, California, 27560, United States
DaVita Hamden
Hamden, Connecticut, 06518, United States
DaVita Middlesex
Middletown, Connecticut, 06457, United States
DaVita New Britain
New Britain, Connecticut, 06052-2016, United States
DaVita Torrington
Torrington, Connecticut, 06790-6268, United States
DaVita Celebration Dialysis
Kissimmee, Florida, 34747, United States
DaVita Troup County Dialysis
La Grange, Georgia, 30240, United States
DaVita Thomaston Dialysis
Thomaston, Georgia, 30286, United States
DaVita Stony Island
Chicago, Illinois, 60617, United States
DaVita West Joliet
Joliet, Illinois, 60435, United States
DaVita Vincennes Dialysis
Vincennes, Indiana, 47591, United States
DaVita Northeast Cambridge
Cambridge, Massachusetts, 02138, United States
DaVita Wellington Circle
Medford, Massachusetts, 02155, United States
DaVita Highland Park
Highland Park, Michigan, 48203, United States
DaVita Arden Hills
Arden Hills, Minnesota, 55112, United States
DaVita Bloomington
Bloomington, Minnesota, 55420, United States
DaVita Burnsville
Burnsville, Minnesota, 55337, United States
DaVita Cass Lake
Cass Lake, Minnesota, 56633, United States
DaVita Coon Rapids
Coon Rapids, Minnesota, 55433, United States
DaVita Cottage Grove
Cottage Grove, Minnesota, 55016, United States
DaVita Moorehead
Dilworth, Minnesota, 56529, United States
DaVita Eden Prairie
Eden Prairie, Minnesota, 55344, United States
DaVita Faribault
Faribault, Minnesota, 55021, United States
DaVita East River Road
Fridley, Minnesota, 55421, United States
DaVita Glencoe
Glencoe, Minnesota, 55336, United States
DaVita Historical Hastings
Hastings, Minnesota, 55033, United States
DaVita Lakeville
Lakeville, Minnesota, 55044, United States
DaVita Maple Grove
Maple Grove, Minnesota, 55369, United States
DaVita Minneapolis Uptown
Minneapolis, Minnesota, 55409, United States
DaVita Minnetonka
Minnetonka, Minnesota, 55345, United States
DaVita New Ulm
New Ulm, Minnesota, 56073, United States
DaVita Northfield
Northfield, Minnesota, 55057, United States
DaVita Redwood Falls
Redwood Falls, Minnesota, 56283, United States
DaVita Richfield
Richfield, Minnesota, 55423, United States
DaVita Rochester
Rochester, Minnesota, 55904, United States
DaVita St. Louis Park
Saint Louis Park, Minnesota, 55426, United States
DaVita St. Paul
Saint Paul, Minnesota, 55103, United States
DaVita Sun Ray
Saint Paul, Minnesota, 55106, United States
DaVita University Riverside
Saint Paul, Minnesota, 55114, United States
DaVita Scott County
Savage, Minnesota, 55378, United States
DaVita West St. Paul
West Saint Paul, Minnesota, 55118, United States
DaVita Wyoming
Wyoming, Minnesota, 55092, United States
DaVita Omaha West Dialysis
Omaha, Nebraska, 68154, United States
DaVita Centennial
Las Vegas, Nevada, 89149, United States
DaVita Pahrump
Pahrump, Nevada, 89048, United States
DaVita Bronx
The Bronx, New York, 10461, United States
DaVita Orchard Park Dialysis
West Seneca, New York, 14127, United States
Burlington Dialysis
Burlington, North Carolina, 27215, United States
North Burlington Dialysis
Burlington, North Carolina, 27217-2928, United States
Durham Dialysis
Durham, North Carolina, 27701, United States
Bull City Dialysis
Durham, North Carolina, 27705, United States
Durham West Dialysis
Durham, North Carolina, 27705, United States
Southpoint Dialysis
Durham, North Carolina, 27713, United States
DaVita Goldsboro South Dialysis
Goldsboro, North Carolina, 27534, United States
Vance County Dialysis
Henderson, North Carolina, 27536, United States
Kerr Lake
Louisburg, North Carolina, 27549, United States
DaVita Reidsville Dialysis
Reidsville, North Carolina, 27320, United States
DaVita Roxboro Dialysis
Roxboro, North Carolina, 27573, United States
DaVita Southern Pines Dialysis
Southern Pines, North Carolina, 28387, United States
DaVita Fargo
Fargo, North Dakota, 58104, United States
DaVita Midwest Fairborn
Fairborn, Ohio, 45324, United States
DaVita Moore
Moore, Oklahoma, 73160, United States
DaVita Tahlequah
Tahlequah, Oklahoma, 74464, United States
DaVita McKeesport West
McKeesport, Pennsylvania, 15132-3953, United States
DaVita Radnor
Radnor, Pennsylvania, 19406, United States
DaVita Blount Dialysis
Maryville, Tennessee, 37804, United States
Renal Center of Waterton
Tyler, Texas, 75703, United States
American Fork Dialysis
American Fork, Utah, 84003, United States
DaVita Bountiful Dialysis
Bountiful, Utah, 84010, United States
DaVita Farmington Bay Dialysis
Layton, Utah, 84041, United States
Payson Dialysis
Payson, Utah, 84651, United States
Provo Dialysis
Provo, Utah, 84604, United States
DaVita Kolff
Salt Lake City, Utah, 84108, United States
DaVita Sandy Dialysis
Sandy City, Utah, 84070, United States
Sandy Dialysis
Taylorsville, Utah, 84129, United States
DaVita Federal Way Dialysis
Federal Way, Washington, 98003, United States
Related Publications (3)
Edmonston D, Isakova T, Dember LM, Waymyers S, Andersen D, Chan KE, Chakraborty H, Wolf M. Higher versus Lower Phosphate Targets for Patients Undergoing In-Center Hemodialysis: A Randomized Controlled Trial. J Am Soc Nephrol. 2025 Dec 1;36(12):2445-2455. doi: 10.1681/ASN.0000000765. Epub 2025 Jul 10.
PMID: 40638247DERIVEDFajol A, Faul C. The Pathologic Actions of Phosphate in CKD. Kidney360. 2025 Apr 17;6(6):1040-1049. doi: 10.34067/KID.0000000820.
PMID: 40241437DERIVEDEdmonston DL, Isakova T, Dember LM, Brunelli S, Young A, Brosch R, Beddhu S, Chakraborty H, Wolf M. Design and Rationale of HiLo: A Pragmatic, Randomized Trial of Phosphate Management for Patients Receiving Maintenance Hemodialysis. Am J Kidney Dis. 2021 Jun;77(6):920-930.e1. doi: 10.1053/j.ajkd.2020.10.008. Epub 2020 Dec 3.
PMID: 33279558DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Trial was early terminated leading to less than 10% of the planned sample size being analyzed.
Results Point of Contact
- Title
- Hrishikesh Chakraborty, DrPH
- Organization
- Duke University School of Medicine
Study Officials
- PRINCIPAL INVESTIGATOR
Myles Wolf, MD, MMSc
Duke Nephrology
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 10, 2019
First Posted
September 19, 2019
Study Start
March 11, 2020
Primary Completion
November 17, 2023
Study Completion
November 17, 2023
Last Updated
April 24, 2025
Results First Posted
January 8, 2025
Record last verified: 2023-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- The Study Protocol SAP will be presented in a methods paper which is planned to be submitted to statistical professionals journals in the coming months. The CSR and the deidentified clinical database will be provided to the NIDDK data repository w/in 3 months of database lock.
- Access Criteria
- Access criteria will be maintained by the NIDDK.
Will share data in accordance with the NIH data sharing guidelines