Trial Outcomes & Findings for HiLo: Pragmatic Trial of Higher vs Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (NCT NCT04095039)
NCT ID: NCT04095039
Last Updated: 2025-04-24
Results Overview
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
TERMINATED
NA
793 participants
up to 27 (enter at enrollment end) - 45 (enter at enrollment start) months
2025-04-24
Participant Flow
Participant milestones
| Measure |
Lo Arm
Patients to titrate blood serum phosphate levels to the standard \<5.5mg/dl
|
Hi Arm
Patients to allow blood serum phosphate levels to rise to 6.5 mg/dl or above
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
|
|---|---|---|
|
Overall Study
STARTED
|
441
|
352
|
|
Overall Study
COMPLETED
|
368
|
261
|
|
Overall Study
NOT COMPLETED
|
73
|
91
|
Reasons for withdrawal
| Measure |
Lo Arm
Patients to titrate blood serum phosphate levels to the standard \<5.5mg/dl
|
Hi Arm
Patients to allow blood serum phosphate levels to rise to 6.5 mg/dl or above
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
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
16
|
|
Overall Study
Transplanted
|
21
|
24
|
|
Overall Study
Transferred to Non-study Facility
|
47
|
44
|
|
Overall Study
Withdrawal from internvention target
|
0
|
2
|
|
Overall Study
Switch to peritoneal dialysis or home hemodialysis
|
2
|
4
|
|
Overall Study
Cacliphylaxis
|
0
|
1
|
|
Overall Study
Pregnancy
|
1
|
0
|
Baseline Characteristics
HiLo: Pragmatic Trial of Higher vs Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis
Baseline characteristics by cohort
| Measure |
Lo Arm
n=441 Participants
Patients to titrate blood serum phosphate levels to the standard \<5.5mg/dl
|
Hi Arm
n=352 Participants
Patients to allow blood serum phosphate levels to rise to 6.5 mg/dl or above
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
|
Total
n=793 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=39 Participants
|
4 Participants
n=41 Participants
|
7 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
382 Participants
n=39 Participants
|
295 Participants
n=41 Participants
|
677 Participants
n=35 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
15 Participants
n=39 Participants
|
19 Participants
n=41 Participants
|
34 Participants
n=35 Participants
|
|
Age, Continuous
|
61.1 years
STANDARD_DEVIATION 14.29 • n=39 Participants
|
59.2 years
STANDARD_DEVIATION 15.00 • n=41 Participants
|
60.3 years
STANDARD_DEVIATION 14.63 • n=35 Participants
|
|
Sex: Female, Male
Female
|
177 Participants
n=39 Participants
|
152 Participants
n=41 Participants
|
329 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
264 Participants
n=39 Participants
|
200 Participants
n=41 Participants
|
464 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
47 Participants
n=39 Participants
|
45 Participants
n=41 Participants
|
92 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=39 Participants
|
12 Participants
n=41 Participants
|
24 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
4 Participants
n=39 Participants
|
6 Participants
n=41 Participants
|
10 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Black or African American
|
181 Participants
n=39 Participants
|
146 Participants
n=41 Participants
|
327 Participants
n=35 Participants
|
|
Race (NIH/OMB)
White
|
180 Participants
n=39 Participants
|
129 Participants
n=41 Participants
|
309 Participants
n=35 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
58 Participants
n=39 Participants
|
48 Participants
n=41 Participants
|
106 Participants
n=35 Participants
|
|
Region of Enrollment
United States
|
441 Participants
n=39 Participants
|
352 Participants
n=41 Participants
|
793 Participants
n=35 Participants
|
|
PCR
|
1.0 g/kg/day
STANDARD_DEVIATION 0.29 • n=39 Participants
|
1.1 g/kg/day
STANDARD_DEVIATION 0.32 • n=41 Participants
|
1.1 g/kg/day
STANDARD_DEVIATION 0.3 • n=35 Participants
|
PRIMARY outcome
Timeframe: up to 27 (enter at enrollment end) - 45 (enter at enrollment start) monthsPopulation: Based on DSMB concerns we adjusted the randomization scheme from cluster-randomized to individual randomization due to concerns of self-selection. At the time that the trial was terminated, only 249 participants were individually randomized so we restricted our analysis to that population.
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
Outcome measures
| Measure |
Lo Arm
n=125 Participants
Patients to titrate blood serum phosphate levels to the standard \<5.5mg/dl
|
Hi Arm
n=124 Participants
Patients to allow blood serum phosphate levels to rise to 6.5 mg/dl or above
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
|
|---|---|---|
|
Hierarchical Composite Mortality and All Cause Hospitalization
All-cause mortality
|
2 total number of events
|
5 total number of events
|
|
Hierarchical Composite Mortality and All Cause Hospitalization
All-cause Hospitalizations
|
98 total number of events
|
128 total number of events
|
SECONDARY outcome
Timeframe: up to 27 (enter at enrollment end) - 45 (enter at enrollment start) monthsPopulation: Based on DSMB concerns we adjusted the randomization scheme from cluster-randomized to individual randomization due to concerns of self-selection. At the time that the trial was terminated, only 249 participants were individually randomized so we restricted our analysis to that population.
Time to all-cause-mortality from baseline for both cluster-randomized and individually randomized cohorts.
Outcome measures
| Measure |
Lo Arm
n=96 Participants
Patients to titrate blood serum phosphate levels to the standard \<5.5mg/dl
|
Hi Arm
n=57 Participants
Patients to allow blood serum phosphate levels to rise to 6.5 mg/dl or above
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
|
|---|---|---|
|
Time to All-cause-mortality
|
1.2 Years
Standard Deviation 0.72
|
1.4 Years
Standard Deviation 0.80
|
SECONDARY outcome
Timeframe: up to 27 (enter at enrollment end) - 45 (enter at enrollment start) monthsPopulation: Total days hospitalized from baseline for both cluster-randomized and individually randomized cohorts. (Data reflects participants with valid, non-missing hospitalization start and end dates)
Total days hospitalized (Data reflects participants with valid, non-missing hospitalization start and end dates.)
Outcome measures
| Measure |
Lo Arm
n=441 Participants
Patients to titrate blood serum phosphate levels to the standard \<5.5mg/dl
|
Hi Arm
n=352 Participants
Patients to allow blood serum phosphate levels to rise to 6.5 mg/dl or above
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
|
|---|---|---|
|
Hospitalization Days
|
27.9 Days
Standard Deviation 29.4
|
35.4 Days
Standard Deviation 46.1
|
SECONDARY outcome
Timeframe: Baseline (days -30 - 0)Population: Serum albumin at baseline for both cluster-randomized and individually randomized cohorts as a marker of diet and nutrition
serum albumin as markers of diet and nutrition.
Outcome measures
| Measure |
Lo Arm
n=441 Participants
Patients to titrate blood serum phosphate levels to the standard \<5.5mg/dl
|
Hi Arm
n=352 Participants
Patients to allow blood serum phosphate levels to rise to 6.5 mg/dl or above
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
|
|---|---|---|
|
Serum Albumin
|
4.1 g/dL
Standard Deviation 0.35
|
4.1 g/dL
Standard Deviation 0.35
|
SECONDARY outcome
Timeframe: Baseline (days -30 - 0)Population: Protein catabolic rate at baseline for both cluster-randomized and individually randomized cohorts as a marker of diet and nutrition
protein catabolic rate (PCR) as markers of diet and nutrition (g/kg/day).
Outcome measures
| Measure |
Lo Arm
n=441 Participants
Patients to titrate blood serum phosphate levels to the standard \<5.5mg/dl
|
Hi Arm
n=352 Participants
Patients to allow blood serum phosphate levels to rise to 6.5 mg/dl or above
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
|
|---|---|---|
|
Protein Catabolic Rate (PCR)
|
1.0 g/kg/day
Standard Deviation 0.29
|
1.1 g/kg/day
Standard Deviation 0.32
|
Adverse Events
Lo Arm
Hi Arm
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Hrishikesh Chakraborty, DrPH
Duke University School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place