Trial Outcomes & Findings for An Extension Study Designed to Assess Effects of Losartan on Proteinuria in Pediatric Populations (MK-0954-326 AM1,EXT1(AM2)) (NCT NCT00568178)
NCT ID: NCT00568178
Last Updated: 2024-05-23
Results Overview
Change in urinary protein excretion, determined as urinary Pr/Cr ratio compared to baseline\*, after approximately twelve weeks of treatment. Baseline is defined as values obtained at Visit 3, Week (-1) during the Single Blind Run-in period.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
306 participants
Primary outcome timeframe
Baseline and Week 12
Results posted on
2024-05-23
Participant Flow
As of March 2011, the study was completed. Phase III First Patient In: 21Jun07; Last Patient Last Visit (double-blind base study): 16Sep08; and (open-label extension): 31Mar11. The study included 52 centers (USA, Europe, Latin America, and Asia) and participants included children aged 6-17 (hypertensive) or 1-17 (normotensive) with proteinuria.
During a 4-week, single-blind run-in participants received losartan placebo (normotensive) or amlodipine (hypertensive) and underwent wash-out of anti-hypertensive agents. To qualify for randomization, participants had to have a mean urine Pr/Cr ratio of ≥0.3 gram/gram (gm/gm) derived from baseline urine samples.
Participant milestones
| Measure |
Losartan Double Blind Normortensive
Normotensive participants who were randomized to losartan.
Losartan dispensed as tablets or suspension depending on participant weight and ability to swallow tablets.
Losartan suspension dosing: 0.7 milligram/kilograms/day (mg/kg/day) titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks. Losartan tablet dosing: 25 mg/day orally titrated to 50 mg/day (participants \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (participants ≥50 kg) for 12 weeks; or losartan placebo.
|
Placebo Double Blind Normotensive
Normotensive participants who were randomized to losartan placebo.
Losartan placebo dispensed as tablets or suspension depending on participant weight and ability to swallow tablets.
Losartan placebo suspension dosing: 0.7 mg/kg/day titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks.
Losartan placebo tablet dosing: 25 mg/day orally titrated to 50 mg/day (participants \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (participants ≥50 kg) for 12 weeks.
|
Losartan Double Blind Hypertensive
Hypertensive patients who were randomized to receive losartan and amlodipine placebo for 12 weeks.
Losartan dispensed as tablets or suspension depending on participant weight and ability to swallow tablets. Amlodipine placebo dispensed as suspension for duration of study.
Losartan suspension dosing: 0.7 milligram/kilograms/day (mg/kg/day) titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks. Amlodipine placebo suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan tablet dosing: 25 mg/day orally titrated to 50 mg/day (participants \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (participants ≥50 kg) for 12 weeks.
|
Amlodipine Double Blind Hypertensive
Hypertensive patients who were randomized to receive amlodipine and losartan placebo for 12 weeks.
Losartan placebo dispensed as tablets or suspension depending on participant weight and ability to swallow tablets.
Losartan placebo suspension dosing: 0.7 mg/kg/day titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks.
Amlodipine suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan placebo tablet dosing: 25 mg/day orally titrated to 50 mg/day (participants \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (participants ≥50 kg) for 12 weeks.
|
Losartan Open Label Extension
Participants were stratified based on assigned treatment in the double-blind treatment phase and were randomized in a 1:1 ratio to either losartan or enalapril.
Dosing of study medication during the extension phase of the study was at the investigator's discretion.
Losartan 25-mg and 50-mg tablets were available for patients able to swallow tablets. For patients unable to swallow tablets, or who weighed \<25 kg, losartan suspension (2.5 mg/ml) was prepared.
|
Enalapril Open Label Extension
Participants were stratified based on assigned treatment in the double-blind treatment phase and were randomized in a 1:1 ratio to either losartan or enalapril.
Dosing of study medication during the extension phase of the study was at the investigator's discretion.
Enalapril 2.5-, 5-, 10-, and 20-mg tablets were available for participants able to swallow tablets. For participants unable to swallow tablets, or who weighed \<25 kg, enalapril suspension (1 mg/mL) was prepared.
|
|---|---|---|---|---|---|---|
|
Double Blind Base Study
STARTED
|
122
|
124
|
30
|
30
|
0
|
0
|
|
Double Blind Base Study
COMPLETED
|
116
|
118
|
29
|
25
|
0
|
0
|
|
Double Blind Base Study
NOT COMPLETED
|
6
|
6
|
1
|
5
|
0
|
0
|
|
Open Label Extension
STARTED
|
0
|
0
|
0
|
0
|
134
|
134
|
|
Open Label Extension
COMPLETED
|
0
|
0
|
0
|
0
|
55
|
54
|
|
Open Label Extension
NOT COMPLETED
|
0
|
0
|
0
|
0
|
79
|
80
|
Reasons for withdrawal
| Measure |
Losartan Double Blind Normortensive
Normotensive participants who were randomized to losartan.
Losartan dispensed as tablets or suspension depending on participant weight and ability to swallow tablets.
Losartan suspension dosing: 0.7 milligram/kilograms/day (mg/kg/day) titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks. Losartan tablet dosing: 25 mg/day orally titrated to 50 mg/day (participants \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (participants ≥50 kg) for 12 weeks; or losartan placebo.
|
Placebo Double Blind Normotensive
Normotensive participants who were randomized to losartan placebo.
Losartan placebo dispensed as tablets or suspension depending on participant weight and ability to swallow tablets.
Losartan placebo suspension dosing: 0.7 mg/kg/day titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks.
Losartan placebo tablet dosing: 25 mg/day orally titrated to 50 mg/day (participants \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (participants ≥50 kg) for 12 weeks.
|
Losartan Double Blind Hypertensive
Hypertensive patients who were randomized to receive losartan and amlodipine placebo for 12 weeks.
Losartan dispensed as tablets or suspension depending on participant weight and ability to swallow tablets. Amlodipine placebo dispensed as suspension for duration of study.
Losartan suspension dosing: 0.7 milligram/kilograms/day (mg/kg/day) titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks. Amlodipine placebo suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan tablet dosing: 25 mg/day orally titrated to 50 mg/day (participants \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (participants ≥50 kg) for 12 weeks.
|
Amlodipine Double Blind Hypertensive
Hypertensive patients who were randomized to receive amlodipine and losartan placebo for 12 weeks.
Losartan placebo dispensed as tablets or suspension depending on participant weight and ability to swallow tablets.
Losartan placebo suspension dosing: 0.7 mg/kg/day titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks.
Amlodipine suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan placebo tablet dosing: 25 mg/day orally titrated to 50 mg/day (participants \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (participants ≥50 kg) for 12 weeks.
|
Losartan Open Label Extension
Participants were stratified based on assigned treatment in the double-blind treatment phase and were randomized in a 1:1 ratio to either losartan or enalapril.
Dosing of study medication during the extension phase of the study was at the investigator's discretion.
Losartan 25-mg and 50-mg tablets were available for patients able to swallow tablets. For patients unable to swallow tablets, or who weighed \<25 kg, losartan suspension (2.5 mg/ml) was prepared.
|
Enalapril Open Label Extension
Participants were stratified based on assigned treatment in the double-blind treatment phase and were randomized in a 1:1 ratio to either losartan or enalapril.
Dosing of study medication during the extension phase of the study was at the investigator's discretion.
Enalapril 2.5-, 5-, 10-, and 20-mg tablets were available for participants able to swallow tablets. For participants unable to swallow tablets, or who weighed \<25 kg, enalapril suspension (1 mg/mL) was prepared.
|
|---|---|---|---|---|---|---|
|
Double Blind Base Study
Adverse Event
|
0
|
2
|
1
|
2
|
0
|
0
|
|
Double Blind Base Study
Lost to Follow-up
|
1
|
0
|
0
|
1
|
0
|
0
|
|
Double Blind Base Study
Physician Decision
|
1
|
1
|
0
|
1
|
0
|
0
|
|
Double Blind Base Study
Protocol Violation
|
3
|
2
|
0
|
0
|
0
|
0
|
|
Double Blind Base Study
Withdrawal by Subject
|
1
|
1
|
0
|
0
|
0
|
0
|
|
Double Blind Base Study
Progressive Disease
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Open Label Extension
Adverse Event
|
0
|
0
|
0
|
0
|
11
|
8
|
|
Open Label Extension
Protocol Violation
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Open Label Extension
Lost to Follow-up
|
0
|
0
|
0
|
0
|
6
|
11
|
|
Open Label Extension
Physician Decision
|
0
|
0
|
0
|
0
|
9
|
8
|
|
Open Label Extension
Pregnancy
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Open Label Extension
Progressive Disease
|
0
|
0
|
0
|
0
|
3
|
1
|
|
Open Label Extension
Termination of Trial
|
0
|
0
|
0
|
0
|
45
|
47
|
|
Open Label Extension
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
4
|
4
|
Baseline Characteristics
An Extension Study Designed to Assess Effects of Losartan on Proteinuria in Pediatric Populations (MK-0954-326 AM1,EXT1(AM2))
Baseline characteristics by cohort
| Measure |
Losartan
n=152 Participants
Four arms combined to 2 groups (losartan \& amlodipine/placebo) for reporting and compared those who took losartan to those who did not (i.e., participants took amlodipine and/or placebo).
"Losartan" group: Normotensives were randomized to losartan and Hypertensives were randomized to losartan \& amlodipine placebo.
Losartan dispensed as tablets or suspension depending on patient weight and ability to swallow tablets. Amlodipine placebo dispensed as suspension for duration of study.
Losartan suspension dosing: 0.7 milligram/kilograms/day (mg/kg/day) titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks. Amlodipine placebo suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan dosing: 25 mg/day orally titrated to 50 mg/day (participants \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (participants ≥50 kg) for 12 weeks.
|
Amlodipine/Placebo
n=154 Participants
"Amlodipine/Placebo" group includes the following: Normotensive patients randomized to losartan. Hypertensive patients randomized to amlodipine and losartan placebo.
Losartan placebo dispensed as tablets or suspension depending on patient weight and ability to swallow tablets. Amlodipine dispensed as suspension for duration of study. Losartan placebo suspension dosing: 0.7 mg/kg/day titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks.
Amlodipine suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan placebo tablet dosing: 25 mg/day orally titrated to 50 mg/day (patients \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (patients ≥50 kg) for 12 weeks.
|
Total
n=306 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
10.4 years
STANDARD_DEVIATION 4.7 • n=5 Participants
|
9.7 years
STANDARD_DEVIATION 4.6 • n=7 Participants
|
10.1 years
STANDARD_DEVIATION 4.7 • n=5 Participants
|
|
Age, Customized
≤6 Years of Age
|
33 participants
n=5 Participants
|
42 participants
n=7 Participants
|
75 participants
n=5 Participants
|
|
Age, Customized
7-12 Years of Age
|
57 participants
n=5 Participants
|
57 participants
n=7 Participants
|
114 participants
n=5 Participants
|
|
Age, Customized
13-17 Years of Age
|
62 participants
n=5 Participants
|
55 participants
n=7 Participants
|
117 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
66 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
130 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
86 Participants
n=5 Participants
|
90 Participants
n=7 Participants
|
176 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
79 Participants
n=5 Participants
|
82 Participants
n=7 Participants
|
161 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
73 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
145 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Hypertensive
Yes
|
30 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Hypertensive
No
|
122 Participants
n=5 Participants
|
124 Participants
n=7 Participants
|
246 Participants
n=5 Participants
|
|
Prior Angiotensin Converting Enzyme Inhibitor /Angiotensin II Type I Receptor Blocker (ACE-I/ARB)Use
Yes
|
83 Participants
n=5 Participants
|
81 Participants
n=7 Participants
|
164 Participants
n=5 Participants
|
|
Prior Angiotensin Converting Enzyme Inhibitor /Angiotensin II Type I Receptor Blocker (ACE-I/ARB)Use
No
|
69 Participants
n=5 Participants
|
73 Participants
n=7 Participants
|
142 Participants
n=5 Participants
|
|
Race
Asian
|
26 participants
n=5 Participants
|
26 participants
n=7 Participants
|
52 participants
n=5 Participants
|
|
Race
Black
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Race
Multi-Racial
|
36 participants
n=5 Participants
|
34 participants
n=7 Participants
|
70 participants
n=5 Participants
|
|
Race
White
|
77 participants
n=5 Participants
|
85 participants
n=7 Participants
|
162 participants
n=5 Participants
|
|
Race
Other
|
8 participants
n=5 Participants
|
4 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Region
United States
|
15 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Region
Outside of United States
|
137 Participants
n=5 Participants
|
144 Participants
n=7 Participants
|
281 Participants
n=5 Participants
|
|
Tanner Stage
Stage I
|
69 Participants
n=5 Participants
|
78 Participants
n=7 Participants
|
147 Participants
n=5 Participants
|
|
Tanner Stage
Stage II
|
26 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
|
Tanner Stage
Stage III
|
22 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Tanner Stage
Stage IV
|
23 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
|
Tanner Stage
Stage V
|
12 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
19.8 kilograms per meter squared (kg/m2)
STANDARD_DEVIATION 5.5 • n=5 Participants
|
19.2 kilograms per meter squared (kg/m2)
STANDARD_DEVIATION 4.2 • n=7 Participants
|
19.5 kilograms per meter squared (kg/m2)
STANDARD_DEVIATION 4.9 • n=5 Participants
|
|
Duration of Hypertension
|
4.8 Years
STANDARD_DEVIATION 4.1 • n=5 Participants
|
6.1 Years
STANDARD_DEVIATION 4.8 • n=7 Participants
|
5.5 Years
STANDARD_DEVIATION 4.5 • n=5 Participants
|
|
Height
|
135.8 Centimeters (cm)
STANDARD_DEVIATION 27.3 • n=5 Participants
|
132.0 Centimeters (cm)
STANDARD_DEVIATION 28.4 • n=7 Participants
|
133.9 Centimeters (cm)
STANDARD_DEVIATION 27.9 • n=5 Participants
|
|
Protein-to-Creatinine Ratio
|
2.2 grams/grams
STANDARD_DEVIATION 2.6 • n=5 Participants
|
2.8 grams/grams
STANDARD_DEVIATION 3.8 • n=7 Participants
|
2.5 grams/grams
STANDARD_DEVIATION 3.3 • n=5 Participants
|
|
Sitting Diastolic Blood Pressure
|
66.8 millimeters of mercury (mm Hg)
STANDARD_DEVIATION 10.7 • n=5 Participants
|
67.8 millimeters of mercury (mm Hg)
STANDARD_DEVIATION 11.6 • n=7 Participants
|
67.3 millimeters of mercury (mm Hg)
STANDARD_DEVIATION 11.2 • n=5 Participants
|
|
Sitting Systolic Blood Pressure
|
106.0 mm Hg
STANDARD_DEVIATION 13.4 • n=5 Participants
|
107.2 mm Hg
STANDARD_DEVIATION 13.8 • n=7 Participants
|
106.6 mm Hg
STANDARD_DEVIATION 13.6 • n=5 Participants
|
|
Weight
|
39.6 Kilograms (kg)
STANDARD_DEVIATION 21.0 • n=5 Participants
|
36.4 Kilograms (kg)
STANDARD_DEVIATION 19.5 • n=7 Participants
|
38.0 Kilograms (kg)
STANDARD_DEVIATION 20.3 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 12Population: Full Analysis Set included all randomized participants who took at least one dose of study drug and had baseline and post randomization measurements available
Change in urinary protein excretion, determined as urinary Pr/Cr ratio compared to baseline\*, after approximately twelve weeks of treatment. Baseline is defined as values obtained at Visit 3, Week (-1) during the Single Blind Run-in period.
Outcome measures
| Measure |
Losartan
n=150 Participants
Participants were randomized in a 1:1 ratio within each stratum: hypertensive patients (6 to 17 years of age) were randomized to either amlodipine or losartan; normotensive patients (1 to 17 years of age) were randomized to either placebo or losartan. Losartan (or placebo) therapy was administered orally, in tablet or suspension form, at an initial dose of approximately 0.7 mg/kg once daily (up to 50 or 100 mg total daily dose, weight-dependent). Participants who were randomized to losartan were assigned to a normotensive or hypertensive group, based on clinical profile.
|
Amlodipine/Placebo
n=152 Participants
"Amlodipine/Placebo" group includes the following: Normotensive patients randomized to losartan placebo. Hypertensive patients randomized to amlodipine and losartan placebo.
Losartan placebo dispensed as tablets or suspension depending on patient weight and ability to swallow tablets. Amlodipine dispensed as suspension for duration of study. Losartan placebo suspension dosing: 0.7 mg/kg/day titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks.
Amlodipine suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan placebo tablet dosing: 25 mg/day orally titrated to 50 mg/day (patients \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (patients ≥50 kg) for 12 weeks.
|
|---|---|---|
|
Double-Blind Treatment Phase: Percent Change From Baseline in Urinary Protein/Creatinine (Pr/Cr) Ratio (gm/gm) at Week 12
|
-35.80 Percent Change in Pr/Cr
Interval -43.11 to -27.55
|
1.37 Percent Change in Pr/Cr
Interval -10.27 to 14.51
|
PRIMARY outcome
Timeframe: Baseline and Month 36Population: Data for analysis was obtained only from participants who had: 1) Baseline measure of Pr/Cr, 2) At least one dose of study drug, and 3) Post randomization measure of Pr/Cr. The number of participants was determined by including only the individuals who satisfied the criteria.
Change in urinary protein excretion, determined as urinary Pr/Cr ratio compared to baseline\*, after approximately three years of treatment. \*The baseline for efficacy data in the extension was defined as the last value obtained in the double-blind treatment phase.
Outcome measures
| Measure |
Losartan
n=130 Participants
Participants were randomized in a 1:1 ratio within each stratum: hypertensive patients (6 to 17 years of age) were randomized to either amlodipine or losartan; normotensive patients (1 to 17 years of age) were randomized to either placebo or losartan. Losartan (or placebo) therapy was administered orally, in tablet or suspension form, at an initial dose of approximately 0.7 mg/kg once daily (up to 50 or 100 mg total daily dose, weight-dependent). Participants who were randomized to losartan were assigned to a normotensive or hypertensive group, based on clinical profile.
|
Amlodipine/Placebo
n=130 Participants
"Amlodipine/Placebo" group includes the following: Normotensive patients randomized to losartan placebo. Hypertensive patients randomized to amlodipine and losartan placebo.
Losartan placebo dispensed as tablets or suspension depending on patient weight and ability to swallow tablets. Amlodipine dispensed as suspension for duration of study. Losartan placebo suspension dosing: 0.7 mg/kg/day titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks.
Amlodipine suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan placebo tablet dosing: 25 mg/day orally titrated to 50 mg/day (patients \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (patients ≥50 kg) for 12 weeks.
|
|---|---|---|
|
Open Label Extension: Percent Change From Baseline of Urinary Pr/Cr Ratio (gm/gm) at Month 36
|
-30.01 Percent Change in Pr/Cr
95% Confidence Interval 5.02 • Interval -44.35 to -11.98
|
-40.45 Percent Change in Pr/Cr
95% Confidence Interval 2.10 • Interval -52.45 to -25.42
|
PRIMARY outcome
Timeframe: Baseline and Month 36Population: Data for analysis was obtained only from participants who had: 1) Baseline measure of Pr/Cr, 2) At least one dose of study drug, and 3) Post randomization measure of Pr/Cr. The number of participants was determined by including only individuals who satisfied the criteria.
The outcome measure of glomerular filtration rate was based on mL/min/1.73m\^2, as determined by the Schwartz formula: GFR = \_\_\_\_\_0.55 x height (cm)\_\_\_\_\_\_\_ divided by serum creatinine (mg/dL) GFR values were compared to the baseline GFR measure. \[Note: For male participants, ages 13 to 17 years, 0.70 was used as the multiplier in place of 0.55\] Baseline in regard to the extension is defined as the last value obtained in the double-blind treatment phase.
Outcome measures
| Measure |
Losartan
n=127 Participants
Participants were randomized in a 1:1 ratio within each stratum: hypertensive patients (6 to 17 years of age) were randomized to either amlodipine or losartan; normotensive patients (1 to 17 years of age) were randomized to either placebo or losartan. Losartan (or placebo) therapy was administered orally, in tablet or suspension form, at an initial dose of approximately 0.7 mg/kg once daily (up to 50 or 100 mg total daily dose, weight-dependent). Participants who were randomized to losartan were assigned to a normotensive or hypertensive group, based on clinical profile.
|
Amlodipine/Placebo
n=127 Participants
"Amlodipine/Placebo" group includes the following: Normotensive patients randomized to losartan placebo. Hypertensive patients randomized to amlodipine and losartan placebo.
Losartan placebo dispensed as tablets or suspension depending on patient weight and ability to swallow tablets. Amlodipine dispensed as suspension for duration of study. Losartan placebo suspension dosing: 0.7 mg/kg/day titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks.
Amlodipine suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan placebo tablet dosing: 25 mg/day orally titrated to 50 mg/day (patients \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (patients ≥50 kg) for 12 weeks.
|
|---|---|---|
|
Open Label Extension: Change From Baseline in Glomerular Filtration Rate (GFR) at Month 36
|
3.3 Change in GFR mL/min1.73m^2
95% Confidence Interval 66.3 • Interval -5.2 to 11.7
|
7.0 Change in GFR mL/min1.73m^2
95% Confidence Interval 53.2 • Interval -1.4 to 15.4
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All-Participants-As-Treated population which included all randomized participants who received at least 1 dose of study therapy, and each participant was counted in the treatment group of the drug they actually received.
Outcome measures
| Measure |
Losartan
n=30 Participants
Participants were randomized in a 1:1 ratio within each stratum: hypertensive patients (6 to 17 years of age) were randomized to either amlodipine or losartan; normotensive patients (1 to 17 years of age) were randomized to either placebo or losartan. Losartan (or placebo) therapy was administered orally, in tablet or suspension form, at an initial dose of approximately 0.7 mg/kg once daily (up to 50 or 100 mg total daily dose, weight-dependent). Participants who were randomized to losartan were assigned to a normotensive or hypertensive group, based on clinical profile.
|
Amlodipine/Placebo
n=30 Participants
"Amlodipine/Placebo" group includes the following: Normotensive patients randomized to losartan placebo. Hypertensive patients randomized to amlodipine and losartan placebo.
Losartan placebo dispensed as tablets or suspension depending on patient weight and ability to swallow tablets. Amlodipine dispensed as suspension for duration of study. Losartan placebo suspension dosing: 0.7 mg/kg/day titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks.
Amlodipine suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan placebo tablet dosing: 25 mg/day orally titrated to 50 mg/day (patients \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (patients ≥50 kg) for 12 weeks.
|
|---|---|---|
|
Double-Blind Treatment Phase: Change From Baseline in Systolic Blood Pressure in Hypertensive Participants at Week 12
|
-5.5 mm Hg
Interval -8.6 to -2.4
|
-0.1 mm Hg
Interval -3.3 to 3.1
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All-Participants-As-Treated population which included all randomized participants who received at least 1 dose of study therapy, and each participant was counted in the treatment group of the drug they actually received
Outcome measures
| Measure |
Losartan
n=30 Participants
Participants were randomized in a 1:1 ratio within each stratum: hypertensive patients (6 to 17 years of age) were randomized to either amlodipine or losartan; normotensive patients (1 to 17 years of age) were randomized to either placebo or losartan. Losartan (or placebo) therapy was administered orally, in tablet or suspension form, at an initial dose of approximately 0.7 mg/kg once daily (up to 50 or 100 mg total daily dose, weight-dependent). Participants who were randomized to losartan were assigned to a normotensive or hypertensive group, based on clinical profile.
|
Amlodipine/Placebo
n=30 Participants
"Amlodipine/Placebo" group includes the following: Normotensive patients randomized to losartan placebo. Hypertensive patients randomized to amlodipine and losartan placebo.
Losartan placebo dispensed as tablets or suspension depending on patient weight and ability to swallow tablets. Amlodipine dispensed as suspension for duration of study. Losartan placebo suspension dosing: 0.7 mg/kg/day titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks.
Amlodipine suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan placebo tablet dosing: 25 mg/day orally titrated to 50 mg/day (patients \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (patients ≥50 kg) for 12 weeks.
|
|---|---|---|
|
Double-Blind Treatment Phase: Change From Baseline in Diastolic Blood Pressure in Hypertensive Participants at Week 12
|
-3.8 mm Hg
Interval -7.0 to -0.7
|
0.8 mm Hg
Interval -2.5 to 4.1
|
Adverse Events
Losartan: Double-Blind Base Study
Serious events: 8 serious events
Other events: 71 other events
Deaths: 0 deaths
Amlodipine/Placebo: Double-Blind Base Study
Serious events: 5 serious events
Other events: 66 other events
Deaths: 0 deaths
Losartan Open-Label Extension
Serious events: 27 serious events
Other events: 83 other events
Deaths: 0 deaths
Enalapril: Open-Label Extension
Serious events: 25 serious events
Other events: 78 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Losartan: Double-Blind Base Study
n=152 participants at risk
Four arms combined to 2 groups (losartan \& amlodipine/placebo) for reporting and compared those who took losartan to those who did not (i.e., participants took amlodipine and/or placebo).
"Losartan" group: Normotensives were randomized to losartan and Hypertensives were randomized to losartan \& amlodipine placebo.
Losartan dispensed as tablets or suspension depending on patient weight and ability to swallow tablets. Amlodipine placebo dispensed as suspension for duration of study.
Losartan suspension dosing: 0.7 milligram/kilograms/day (mg/kg/day) titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks. Amlodipine placebo suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan dosing: 25 mg/day orally titrated to 50 mg/day (participants \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (participants ≥50 kg) for 12 weeks.
|
Amlodipine/Placebo: Double-Blind Base Study
n=154 participants at risk
"Amlodipine/Placebo" group includes the following: Normotensive patients randomized to losartan placebo. Hypertensive patients randomized to amlodipine and losartan placebo.
Losartan placebo dispensed as tablets or suspension depending on patient weight and ability to swallow tablets. Amlodipine dispensed as suspension for duration of study. Losartan placebo suspension dosing: 0.7 mg/kg/day titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks.
Amlodipine suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan placebo tablet dosing: 25 mg/day orally titrated to 50 mg/day (patients \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (patients ≥50 kg) for 12 weeks.
|
Losartan Open-Label Extension
n=134 participants at risk
Please note that the open label participant population was derived exclusively from the original base study population. There was no additional recruitment.
Participants were randomized to either losartan or enalapril, administered in an unblinded fashion (placebo was not used) for the duration of the study. The maximum dose of losartan was 50 mg/day (if the participant weighed \<50 kg) or 100 mg/day (if the participant weighed ≥50 kg) Losartan 25-mg and 50-mg tablets were available for participants able to swallow tablets, and losartan suspension (2.5 mg/ml) was prepared for participants unable to swallow tablets, or for those who weighed \<25 kg.
|
Enalapril: Open-Label Extension
n=134 participants at risk
Please note that the open label participant population was derived exclusively from the original base study population. There was no additional recruitment.
Participants were randomized to either losartan or enalapril, administered in an unblinded fashion (placebo was not used) for the duration of the study. The maximum specified dose of enalapril was 40 mg/day. For participants unable to swallow tablets, or for those who weighed \<25 kg, enalapril suspension (1 mg/mL) was prepared. The starting dose of drug and any adjustments during the open-label period were at the discretion of the investigator.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/152
|
0.00%
0/154
|
1.5%
2/134 • Number of events 2
|
0.00%
0/134
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Congenital, familial and genetic disorders
Lipomeningocele
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Congenital, familial and genetic disorders
Renal hypoplasia
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
1.5%
2/134 • Number of events 2
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
General disorders
Pyrexia
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Infections and infestations
Appendicitis
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.75%
1/134 • Number of events 1
|
|
Infections and infestations
Arthritis bacterial
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Infections and infestations
Bronchitis
|
0.66%
1/152 • Number of events 1
|
0.65%
1/154 • Number of events 1
|
0.00%
0/134
|
0.00%
0/134
|
|
Infections and infestations
Gastroenteritis
|
0.66%
1/152 • Number of events 1
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.75%
1/134 • Number of events 1
|
|
Infections and infestations
Helicobacter infection
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Infections and infestations
Herpangina
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Infections and infestations
Peritonitis bacterial
|
0.66%
1/152 • Number of events 1
|
0.00%
0/154
|
0.00%
0/134
|
0.00%
0/134
|
|
Infections and infestations
Pneumonia
|
0.00%
0/152
|
0.00%
0/154
|
1.5%
2/134 • Number of events 2
|
2.2%
3/134 • Number of events 3
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/152
|
0.00%
0/154
|
2.2%
3/134 • Number of events 4
|
0.00%
0/134
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Infections and infestations
Sepsis
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Infections and infestations
Sinusitis
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.75%
1/134 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/152
|
1.3%
2/154 • Number of events 2
|
1.5%
2/134 • Number of events 2
|
0.75%
1/134 • Number of events 1
|
|
Infections and infestations
Varicella
|
0.66%
1/152 • Number of events 1
|
0.00%
0/154
|
0.00%
0/134
|
0.00%
0/134
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Injury, poisoning and procedural complications
Ulna fracture
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Investigations
Blood creatinine increased
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.75%
1/134 • Number of events 1
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Metabolism and nutrition disorders
Obesity
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus
|
0.66%
1/152 • Number of events 1
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
2.2%
3/134 • Number of events 4
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma
|
0.66%
1/152 • Number of events 1
|
0.00%
0/154
|
0.00%
0/134
|
0.00%
0/134
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma
|
0.66%
1/152 • Number of events 1
|
0.00%
0/154
|
0.00%
0/134
|
0.00%
0/134
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lung
|
0.66%
1/152 • Number of events 1
|
0.00%
0/154
|
0.00%
0/134
|
0.00%
0/134
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastasis
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Nervous system disorders
Altered state of consciousness
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Nervous system disorders
Aphasia
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Nervous system disorders
Convulsion
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
1.5%
2/134 • Number of events 2
|
|
Nervous system disorders
Encephalitis
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Nervous system disorders
Intracranial pressure increased
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Psychiatric disorders
Somatoform disorder neurologic
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Renal and urinary disorders
Glomerulonephritis
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Renal and urinary disorders
Glomerulonephritis membranoproliferative
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/152
|
0.00%
0/154
|
1.5%
2/134 • Number of events 2
|
0.75%
1/134 • Number of events 1
|
|
Renal and urinary disorders
Hydronephrosis
|
0.66%
1/152 • Number of events 1
|
0.00%
0/154
|
0.00%
0/134
|
0.00%
0/134
|
|
Renal and urinary disorders
Lupus nephritis
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Renal and urinary disorders
Nephrotic syndrome
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/152
|
0.65%
1/154 • Number of events 1
|
0.75%
1/134 • Number of events 1
|
0.75%
1/134 • Number of events 1
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/152
|
0.00%
0/154
|
2.2%
3/134 • Number of events 3
|
1.5%
2/134 • Number of events 2
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/152
|
0.00%
0/154
|
1.5%
2/134 • Number of events 2
|
0.75%
1/134 • Number of events 1
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/152
|
0.65%
1/154 • Number of events 1
|
0.00%
0/134
|
0.00%
0/134
|
|
Vascular disorders
Hypotension
|
0.00%
0/152
|
0.00%
0/154
|
0.75%
1/134 • Number of events 1
|
0.00%
0/134
|
|
Vascular disorders
Hypovolaemic shock
|
0.00%
0/152
|
0.00%
0/154
|
0.00%
0/134
|
0.75%
1/134 • Number of events 1
|
Other adverse events
| Measure |
Losartan: Double-Blind Base Study
n=152 participants at risk
Four arms combined to 2 groups (losartan \& amlodipine/placebo) for reporting and compared those who took losartan to those who did not (i.e., participants took amlodipine and/or placebo).
"Losartan" group: Normotensives were randomized to losartan and Hypertensives were randomized to losartan \& amlodipine placebo.
Losartan dispensed as tablets or suspension depending on patient weight and ability to swallow tablets. Amlodipine placebo dispensed as suspension for duration of study.
Losartan suspension dosing: 0.7 milligram/kilograms/day (mg/kg/day) titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks. Amlodipine placebo suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan dosing: 25 mg/day orally titrated to 50 mg/day (participants \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (participants ≥50 kg) for 12 weeks.
|
Amlodipine/Placebo: Double-Blind Base Study
n=154 participants at risk
"Amlodipine/Placebo" group includes the following: Normotensive patients randomized to losartan placebo. Hypertensive patients randomized to amlodipine and losartan placebo.
Losartan placebo dispensed as tablets or suspension depending on patient weight and ability to swallow tablets. Amlodipine dispensed as suspension for duration of study. Losartan placebo suspension dosing: 0.7 mg/kg/day titrated at 2 weeks to 1.4 mg/kg/day orally (maximum 50 mg if \<50 kg or 100 mg if ≥50 kg) for 12 weeks.
Amlodipine suspension dosing: starting dose 0.05 or 0.1 titrated to 0.2 mg/kg/day orally (max 5 mg/day) after 2 weeks if necessary to control blood pressure for 12 weeks. Losartan placebo tablet dosing: 25 mg/day orally titrated to 50 mg/day (patients \<50 kg) OR 50 mg/day orally titrated to 100 mg/day (patients ≥50 kg) for 12 weeks.
|
Losartan Open-Label Extension
n=134 participants at risk
Please note that the open label participant population was derived exclusively from the original base study population. There was no additional recruitment.
Participants were randomized to either losartan or enalapril, administered in an unblinded fashion (placebo was not used) for the duration of the study. The maximum dose of losartan was 50 mg/day (if the participant weighed \<50 kg) or 100 mg/day (if the participant weighed ≥50 kg) Losartan 25-mg and 50-mg tablets were available for participants able to swallow tablets, and losartan suspension (2.5 mg/ml) was prepared for participants unable to swallow tablets, or for those who weighed \<25 kg.
|
Enalapril: Open-Label Extension
n=134 participants at risk
Please note that the open label participant population was derived exclusively from the original base study population. There was no additional recruitment.
Participants were randomized to either losartan or enalapril, administered in an unblinded fashion (placebo was not used) for the duration of the study. The maximum specified dose of enalapril was 40 mg/day. For participants unable to swallow tablets, or for those who weighed \<25 kg, enalapril suspension (1 mg/mL) was prepared. The starting dose of drug and any adjustments during the open-label period were at the discretion of the investigator.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/152
|
0.00%
0/154
|
8.2%
11/134 • Number of events 12
|
6.0%
8/134 • Number of events 10
|
|
Gastrointestinal disorders
Diarrhoea
|
5.3%
8/152 • Number of events 10
|
4.5%
7/154 • Number of events 7
|
9.0%
12/134 • Number of events 15
|
5.2%
7/134 • Number of events 9
|
|
Gastrointestinal disorders
Vomiting
|
3.9%
6/152 • Number of events 8
|
2.6%
4/154 • Number of events 4
|
11.9%
16/134 • Number of events 22
|
3.0%
4/134 • Number of events 4
|
|
General disorders
Pyrexia
|
3.9%
6/152 • Number of events 6
|
1.3%
2/154 • Number of events 2
|
6.0%
8/134 • Number of events 10
|
5.2%
7/134 • Number of events 9
|
|
Infections and infestations
Bronchitis
|
5.9%
9/152 • Number of events 10
|
5.2%
8/154 • Number of events 8
|
6.7%
9/134 • Number of events 13
|
6.7%
9/134 • Number of events 10
|
|
Infections and infestations
Gastroenteritis
|
2.0%
3/152 • Number of events 3
|
1.9%
3/154 • Number of events 3
|
6.7%
9/134 • Number of events 15
|
4.5%
6/134 • Number of events 10
|
|
Infections and infestations
Influenza
|
1.3%
2/152 • Number of events 2
|
0.65%
1/154 • Number of events 1
|
2.2%
3/134 • Number of events 4
|
5.2%
7/134 • Number of events 9
|
|
Infections and infestations
Nasopharyngitis
|
15.8%
24/152 • Number of events 28
|
12.3%
19/154 • Number of events 22
|
23.1%
31/134 • Number of events 40
|
14.9%
20/134 • Number of events 28
|
|
Infections and infestations
Pharyngitis
|
3.9%
6/152 • Number of events 6
|
3.9%
6/154 • Number of events 7
|
15.7%
21/134 • Number of events 44
|
14.9%
20/134 • Number of events 31
|
|
Infections and infestations
Pharyngotonsillitis
|
0.00%
0/152
|
0.65%
1/154 • Number of events 1
|
6.0%
8/134 • Number of events 11
|
4.5%
6/134 • Number of events 6
|
|
Infections and infestations
Upper respiratory tract infection
|
4.6%
7/152 • Number of events 8
|
5.8%
9/154 • Number of events 13
|
11.2%
15/134 • Number of events 50
|
6.7%
9/134 • Number of events 20
|
|
Infections and infestations
Urinary tract infection
|
1.3%
2/152 • Number of events 2
|
1.9%
3/154 • Number of events 3
|
7.5%
10/134 • Number of events 14
|
7.5%
10/134 • Number of events 15
|
|
Investigations
Urine protein/creatinine ratio increased
|
0.00%
0/152
|
0.00%
0/154
|
6.0%
8/134 • Number of events 10
|
4.5%
6/134 • Number of events 8
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.66%
1/152 • Number of events 1
|
0.00%
0/154
|
3.0%
4/134 • Number of events 5
|
6.7%
9/134 • Number of events 15
|
|
Nervous system disorders
Dizziness
|
3.9%
6/152 • Number of events 6
|
1.9%
3/154 • Number of events 3
|
2.2%
3/134 • Number of events 3
|
5.2%
7/134 • Number of events 10
|
|
Nervous system disorders
Headache
|
8.6%
13/152 • Number of events 24
|
13.0%
20/154 • Number of events 31
|
5.2%
7/134 • Number of events 19
|
9.0%
12/134 • Number of events 23
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/152
|
0.65%
1/154 • Number of events 1
|
6.0%
8/134 • Number of events 9
|
2.2%
3/134 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.3%
5/152 • Number of events 6
|
3.9%
6/154 • Number of events 8
|
6.0%
8/134 • Number of events 9
|
8.2%
11/134 • Number of events 13
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER