Trial Outcomes & Findings for Losartan to Reverse Sickle Nephropathy (NCT NCT01479439)
NCT ID: NCT01479439
Last Updated: 2020-09-29
Results Overview
Number of participants who have a ≥25% reduction in urinary albumin-to-creatinine ratio (UACR) from baseline to 6 months. This is a categorical outcome (yes/no). We hypothesized and pre-specified that ≥30% of the subjects in the microalbuminuria group would meet this outcome.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
36 participants
Primary outcome timeframe
Baseline and 6 months
Results posted on
2020-09-29
Participant Flow
This was a multicenter, phase 2, open-label study of losartan for sickle cell nephropathy. Participants were enrolled at nine centers in the United States between 2012 and 2015.
Concomitant treatment with hydroxyurea was allowed, but the dose must have been stable in the 3 months preceding enrollment. Participants were allocated to three pre-specified groups defined by baseline urinary albumin-to-creatinine ratio (UACR).
Participant milestones
| Measure |
Losartan - No Albuminuria
Baseline urinary albumin-to-creatinine ratio (UACR) \<30 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
Losartan - Microalbuminuria
Baseline urinary albumin-to-creatinine ratio (UACR) 30-300 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
Losartan - Macroalbuminuria
Baseline urinary albumin-to-creatinine ratio (UACR) \>300 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
|---|---|---|---|
|
Overall Study
STARTED
|
15
|
13
|
8
|
|
Overall Study
COMPLETED
|
14
|
12
|
6
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
2
|
Reasons for withdrawal
| Measure |
Losartan - No Albuminuria
Baseline urinary albumin-to-creatinine ratio (UACR) \<30 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
Losartan - Microalbuminuria
Baseline urinary albumin-to-creatinine ratio (UACR) 30-300 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
Losartan - Macroalbuminuria
Baseline urinary albumin-to-creatinine ratio (UACR) \>300 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
|
Overall Study
Protocol Violation
|
0
|
0
|
2
|
Baseline Characteristics
Losartan to Reverse Sickle Nephropathy
Baseline characteristics by cohort
| Measure |
Losartan - No Albuminuria
n=14 Participants
Baseline urinary albumin-to-creatinine ratio (UACR) \<30 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
Losartan - Microalbuminuria
n=12 Participants
Baseline urinary albumin-to-creatinine ratio (UACR) 30-300 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
Losartan - Macroalbuminuria
n=6 Participants
Baseline urinary albumin-to-creatinine ratio (UACR) \>300 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Continuous
|
14.6 years
STANDARD_DEVIATION 4.9 • n=5 Participants
|
28.6 years
STANDARD_DEVIATION 16.6 • n=7 Participants
|
38.8 years
STANDARD_DEVIATION 18.5 • n=5 Participants
|
24.4 years
STANDARD_DEVIATION 88.8 • n=4 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
14 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
14 participants
n=5 Participants
|
12 participants
n=7 Participants
|
6 participants
n=5 Participants
|
32 participants
n=4 Participants
|
|
Urinary albumin-to-creatinine ratio (UACR) (mg/g)
|
8.5 mg/g
STANDARD_DEVIATION 4.9 • n=5 Participants
|
121 mg/g
STANDARD_DEVIATION 86.6 • n=7 Participants
|
815 mg/g
STANDARD_DEVIATION 335.6 • n=5 Participants
|
202 mg/g
STANDARD_DEVIATION 333.8 • n=4 Participants
|
|
Creatinine clearance by 24h Urine Collection
|
146 mL/min/1.73m^2
STANDARD_DEVIATION 228 • n=5 Participants
|
172 mL/min/1.73m^2
STANDARD_DEVIATION 204 • n=7 Participants
|
108 mL/min/1.73m^2
STANDARD_DEVIATION 46.5 • n=5 Participants
|
150 mL/min/1.73m^2
STANDARD_DEVIATION 56.5 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and 6 monthsNumber of participants who have a ≥25% reduction in urinary albumin-to-creatinine ratio (UACR) from baseline to 6 months. This is a categorical outcome (yes/no). We hypothesized and pre-specified that ≥30% of the subjects in the microalbuminuria group would meet this outcome.
Outcome measures
| Measure |
Losartan - No Albuminuria
n=14 Participants
Baseline urinary albumin-to-creatinine ratio (UACR) \<30 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
Losartan - Microalbuminuria
n=12 Participants
Baseline urinary albumin-to-creatinine ratio (UACR) 30-300 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
Losartan - Macroalbuminuria
n=6 Participants
Baseline urinary albumin-to-creatinine ratio (UACR) \>300 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
|---|---|---|---|
|
Categorical Change in Urinary Albumin-to-creatinine Ratio (UACR) From Baseline
|
1 Participants
|
7 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Baseline and 6 monthsFold-change in UACR from baseline
Outcome measures
| Measure |
Losartan - No Albuminuria
n=14 Participants
Baseline urinary albumin-to-creatinine ratio (UACR) \<30 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
Losartan - Microalbuminuria
n=12 Participants
Baseline urinary albumin-to-creatinine ratio (UACR) 30-300 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
Losartan - Macroalbuminuria
n=6 Participants
Baseline urinary albumin-to-creatinine ratio (UACR) \>300 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
|---|---|---|---|
|
Change in UACR
|
0.08 Fold-change
Interval -0.07 to 1.06
|
-0.46 Fold-change
Interval -0.75 to 2.53
|
-0.74 Fold-change
Interval -0.91 to -0.17
|
SECONDARY outcome
Timeframe: Baseline and 6 monthsFold-change in creatinine clearance by 24h urine collection (GFR-CrCl) from baseline
Outcome measures
| Measure |
Losartan - No Albuminuria
n=14 Participants
Baseline urinary albumin-to-creatinine ratio (UACR) \<30 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
Losartan - Microalbuminuria
n=12 Participants
Baseline urinary albumin-to-creatinine ratio (UACR) 30-300 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
Losartan - Macroalbuminuria
n=6 Participants
Baseline urinary albumin-to-creatinine ratio (UACR) \>300 mg/g.
All participants in this study in all arms were treated with losartan using the same dosing regimen. Study arms are only differentiated by baseline UACR.
|
|---|---|---|---|
|
Change in Creatinine Clearance
|
0.06 Fold-change
Interval -0.1 to 0.44
|
0.12 Fold-change
Interval -0.34 to 0.26
|
0.05 Fold-change
Interval -0.01 to 0.33
|
Adverse Events
No Albuminuria (NoA)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Microalbuminuria (MicroA)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Macroalbuminuria
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
No Albuminuria (NoA)
n=14 participants at risk
Baseline urinary albumin-to-creatinine ratio (UACR) \<30 mg/g
|
Microalbuminuria (MicroA)
n=12 participants at risk
Baseline urinary albumin-to-creatinine ratio (UACR) 30-300 mg/g
|
Macroalbuminuria
n=6 participants at risk
Baseline urinary albumin-to-creatinine ratio (UACR) \>300 mg/g
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Muscle Cramps
|
0.00%
0/14
|
8.3%
1/12 • Number of events 1
|
0.00%
0/6
|
|
Renal and urinary disorders
Increase in serum creatinine >50% from baseline
|
0.00%
0/14
|
8.3%
1/12 • Number of events 1
|
0.00%
0/6
|
|
Renal and urinary disorders
Decline in GFR >25% from baseline
|
0.00%
0/14
|
8.3%
1/12 • Number of events 1
|
0.00%
0/6
|
Additional Information
Dr. Charles Quinn
Cincinnati Children's Hospital Medical Center
Phone: 5138033086
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place