Trial Outcomes & Findings for ALiskiren or Losartan Effects on bioMARKers of Myocardial Remodeling (NCT NCT01176032)
NCT ID: NCT01176032
Last Updated: 2014-07-24
Results Overview
PICP is a measure of blood concentration of procollagen I carboxy-terminal propeptide (PICP), a peptide released from the myocardium when procollagen is converted to type I collagen. This biomarker exhibits good specificity and sensitivity for identifying myocardial fibrosis in hypertension.
COMPLETED
PHASE4
74 participants
Baseline, Week 36
2014-07-24
Participant Flow
Participant milestones
| Measure |
Aliskiren
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
37
|
37
|
|
Overall Study
Intention-to-treat (ITT) Population
|
32
|
37
|
|
Overall Study
COMPLETED
|
31
|
36
|
|
Overall Study
NOT COMPLETED
|
6
|
1
|
Reasons for withdrawal
| Measure |
Aliskiren
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Unsatisfactory therapeutic effect
|
0
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Informed consent withdrawn
|
3
|
0
|
|
Overall Study
Other
|
1
|
0
|
Baseline Characteristics
ALiskiren or Losartan Effects on bioMARKers of Myocardial Remodeling
Baseline characteristics by cohort
| Measure |
Aliskiren
n=32 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=37 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Total
n=69 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.34 Years
STANDARD_DEVIATION 9.34 • n=5 Participants
|
58.05 Years
STANDARD_DEVIATION 10.34 • n=7 Participants
|
59.12 Years
STANDARD_DEVIATION 9.88 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment.
PICP is a measure of blood concentration of procollagen I carboxy-terminal propeptide (PICP), a peptide released from the myocardium when procollagen is converted to type I collagen. This biomarker exhibits good specificity and sensitivity for identifying myocardial fibrosis in hypertension.
Outcome measures
| Measure |
Aliskiren
n=32 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=37 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in C-terminal Propeptide of Procollagen Type I (PICP)
|
-5.22 ug/l
Standard Deviation 20.37
|
-4.25 ug/l
Standard Deviation 24.80
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment. Patients with both baseline and week 36 assessment were included in this analysis.
The plasma level of biomarkers parameters used to measure improvement in left ventricular (LV) function or reduction in left ventricular mass index (LVMI). The following biomarkers were analyzed: cardiotrophin-1 (CT-1), matrix metalloproteinase-1 (MMP-1); tissue inhibitor of MMPs (TIMP-1); annexin A5 (AnxA5); N-terminal prohormone of B-type natriuretic peptide (NT-proBNP)
Outcome measures
| Measure |
Aliskiren
n=32 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=37 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in Biomarkers in Heart Disease
cardiotrophin-1 (CT-1) (n=32,37)
|
-169.15 ng/ml
Standard Deviation 561.51
|
-128.23 ng/ml
Standard Deviation 568.02
|
—
|
—
|
|
Change From Baseline in Biomarkers in Heart Disease
matrix metalloproteinase-1 (MMP-1) (n=32,37)
|
5.93 ng/ml
Standard Deviation 13.33
|
5.51 ng/ml
Standard Deviation 9.58
|
—
|
—
|
|
Change From Baseline in Biomarkers in Heart Disease
tissue inhibitor of MMPs (TIMP-1) (n=32,37)
|
-0.70 ng/ml
Standard Deviation 59.18
|
9.15 ng/ml
Standard Deviation 42.58
|
—
|
—
|
|
Change From Baseline in Biomarkers in Heart Disease
annexin A5 (AnxA5) (n=31,37)
|
-0.98 ng/ml
Standard Deviation 7.33
|
-1.21 ng/ml
Standard Deviation 4.75
|
—
|
—
|
|
Change From Baseline in Biomarkers in Heart Disease
NT-proBNP (n=31,34)
|
18.66 ng/ml
Standard Deviation 165.21
|
-7.55 ng/ml
Standard Deviation 38.11
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment. Patients with both baseline and week 36 assessment were included in this analysis.
The plasma level of biomarker parameter (aldosterone (Aldo)) used to measure improvement in left ventricular (LV) function or reduction in left ventricular mass index (LVMI)
Outcome measures
| Measure |
Aliskiren
n=32 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=37 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in Biomarker Such as Aldosterone (Aldo) in Heart Disease
|
-1.81 ng/dl
Standard Deviation 27.78
|
-7.90 ng/dl
Standard Deviation 76.35
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment. Patients with both baseline and week 36 assessment were included in this analysis.
Reductions in the following measurements were analysed between the baseline visit and the final visit: LV end-diastolic volume by Simpson's rule, and LV end-systolic volume by Simpson's rule
Outcome measures
| Measure |
Aliskiren
n=32 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=37 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in Left Ventricular (LV) Function, LV End-diastolic Volume by Simpson's Rule, and LV End-systolic Volume by Simpson's Rule
LV end-diastolic volume (n=22,34)
|
2.30 ml
Standard Deviation 35.65
|
0.54 ml
Standard Deviation 33.19
|
—
|
—
|
|
Change From Baseline in Left Ventricular (LV) Function, LV End-diastolic Volume by Simpson's Rule, and LV End-systolic Volume by Simpson's Rule
LV end-systolic volume (n=22,34)
|
-0.92 ml
Standard Deviation 12.24
|
0.64 ml
Standard Deviation 21.01
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment. Patients with both baseline and week 36 assessment were included in this analysis.
Reductions in the following measurements were analysed between the baseline visit and the final visit: LV ejection fraction (Teicholz), and LV ejection fraction (Simpson)
Outcome measures
| Measure |
Aliskiren
n=32 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=37 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in Left Ventricular (LV) Function, LV Ejection Fraction (Teicholz), and LV Ejection Fraction (Simpson)
LV ejection fraction Teicholz(n=29,36)
|
0.00 Percent
Standard Deviation 0.11
|
0.01 Percent
Standard Deviation 0.08
|
—
|
—
|
|
Change From Baseline in Left Ventricular (LV) Function, LV Ejection Fraction (Teicholz), and LV Ejection Fraction (Simpson)
LV ejection fraction Simpson(n=22,34)
|
0.02 Percent
Standard Deviation 0.14
|
0.00 Percent
Standard Deviation 0.11
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment. Patients with both baseline and week 36 assessment were included in this analysis.
Reductions in the following measurements were analysed between the baseline visit and the final visit: LA diameter
Outcome measures
| Measure |
Aliskiren
n=24 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=30 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in Left Ventricular (LV) Function, LA (Left Atrium) Diameter
|
-0.13 mm/m^2
Standard Deviation 1.17
|
-0.22 mm/m^2
Standard Deviation 0.98
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment. Patients with both baseline and week 36 assessment were included in this analysis.
Reductions in the following measurements were analysed between the baseline visit and the final visit: left atrial volume (biplane Simpson's method)
Outcome measures
| Measure |
Aliskiren
n=12 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=22 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in Left Ventricular (LV) Function, Left Atrial Volume (Biplane Simpson's Method)
|
-0.55 cm3/m^2
Standard Deviation 17.94
|
-2.27 cm3/m^2
Standard Deviation 26.46
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment
Echocardiogram was performed at week 1 and at week 36. Reduction in LVMI is defined as the difference between the LVMI at the final visit and the baseline LVMI
Outcome measures
| Measure |
Aliskiren
n=32 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=37 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in Reduction of Left Ventricular Mass Index (LVMI)
|
-8.05 g/m^2
Standard Deviation 18.98
|
-7.96 g/m^2
Standard Deviation 18.69
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment. Patients with both baseline and week 36 assessment were included in this analysis.
The plasma level of biomarkers parameters used to measure improvement in left ventricular (LV) function or reduction in left ventricular mass index (LVMI). The following biomarkers were analyzed: cardiotrophin-1 (CT-1), matrix metalloproteinase-1 (MMP-1); tissue inhibitor of MMPs (TIMP-1); annexin A5 (AnxA5); N-terminal prohormone of B-type natriuretic peptide (NT-proBNP)
Outcome measures
| Measure |
Aliskiren
n=15 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=17 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
n=16 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
n=21 Participants
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in Combination of Aliskiren With Amlodipine in Biomarkers of Heart Disease.
CT-1(n=15,17,16,21)
|
-289.18 ng/ml
Standard Deviation 608.91
|
-63.23 ng/ml
Standard Deviation 510.91
|
156.89 ng/ml
Standard Deviation 599.29
|
-345.47 ng/ml
Standard Deviation 443.63
|
|
Change From Baseline in Combination of Aliskiren With Amlodipine in Biomarkers of Heart Disease.
ANXA5 (n=15,16,16,21)
|
-1.24 ng/ml
Standard Deviation 3.70
|
-0.74 ng/ml
Standard Deviation 9.73
|
-1.73 ng/ml
Standard Deviation 4.21
|
-0.81 ng/ml
Standard Deviation 5.20
|
|
Change From Baseline in Combination of Aliskiren With Amlodipine in Biomarkers of Heart Disease.
MMP-1(n=15,17,16,21)
|
7.00 ng/ml
Standard Deviation 10.28
|
4.99 ng/ml
Standard Deviation 15.80
|
5.47 ng/ml
Standard Deviation 7.88
|
5.54 ng/ml
Standard Deviation 10.89
|
|
Change From Baseline in Combination of Aliskiren With Amlodipine in Biomarkers of Heart Disease.
TIMP-1 (n=15,17,16,21)
|
-10.01 ng/ml
Standard Deviation 73.00
|
7.51 ng/ml
Standard Deviation 44.38
|
21.38 ng/ml
Standard Deviation 38.40
|
-0.16 ng/ml
Standard Deviation 44.13
|
|
Change From Baseline in Combination of Aliskiren With Amlodipine in Biomarkers of Heart Disease.
NT-proBNP (n=15,16,15,19)
|
21.00 ng/ml
Standard Deviation 214.06
|
16.46 ng/ml
Standard Deviation 108.69
|
-3.68 ng/ml
Standard Deviation 23.78
|
-10.60 ng/ml
Standard Deviation 46.91
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment. Patients with both baseline and week 36 assessment were included in this analysis.
The plasma level of biomarker parameter plasma aldosterone used to measure improvement in left ventricular (LV) function or reduction in left ventricular mass index (LVMI).
Outcome measures
| Measure |
Aliskiren
n=15 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=17 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
n=16 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
n=21 Participants
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in Biomarker Such as Aldosterone (Aldo) in Heart Disease in Combination of Aliskiren With Amlodipine
|
2.81 ng/dl
Standard Deviation 21.36
|
-5.89 ng/dl
Standard Deviation 32.54
|
-3.12 ng/dl
Standard Deviation 32.45
|
-11.55 ng/dl
Standard Deviation 98.35
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment. Patients with both baseline and week 36 assessment were included in this analysis.
Reductions in the following measurements were analysed between the baseline visit and the final visit: LV end-diastolic volume by Simpson's rule, and LV end-systolic volume by Simpson's rule
Outcome measures
| Measure |
Aliskiren
n=15 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=17 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
n=16 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
n=21 Participants
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in Left Ventricular (LV) Function, LV End-diastolic Volume by Simpson's Rule, and LV End-systolic Volume by Simpson's Rule in Combination of Aliskiren With Amlodipine
LV end-diastolic volume (n=11,11,15,19)
|
6.60 ml
Standard Deviation 40.43
|
-2.00 ml
Standard Deviation 31.51
|
5.01 ml
Standard Deviation 38.15
|
-2.98 ml
Standard Deviation 29.30
|
|
Change From Baseline in Left Ventricular (LV) Function, LV End-diastolic Volume by Simpson's Rule, and LV End-systolic Volume by Simpson's Rule in Combination of Aliskiren With Amlodipine
LV end-systolic volume (n=11,11, 15,19)
|
-2.93 ml
Standard Deviation 13.24
|
1.09 ml
Standard Deviation 11.44
|
6.11 ml
Standard Deviation 23.82
|
-3.69 ml
Standard Deviation 17.97
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment. Patients with both baseline and week 36 assessment were included in this analysis.
Reductions in the following measurements were analysed between the baseline visit and the final visit: LV ejection fraction (Teicholz), and LV ejection fraction (Simpson)
Outcome measures
| Measure |
Aliskiren
n=15 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=17 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
n=16 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
n=21 Participants
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in Left Ventricular (LV) Function, LV Ejection Fraction (Teicholz), and LV Ejection Fraction (Simpson) in Combination of Aliskiren With Amlodipine
LV ejection fraction Teicholz (n=14,15,16,20)
|
0.00 Percent
Standard Deviation 0.09
|
-0.00 Percent
Standard Deviation 0.13
|
-0.00 Percent
Standard Deviation 0.07
|
0.01 Percent
Standard Deviation 0.09
|
|
Change From Baseline in Left Ventricular (LV) Function, LV Ejection Fraction (Teicholz), and LV Ejection Fraction (Simpson) in Combination of Aliskiren With Amlodipine
LV ejection fraction Simpson(n=11,11,15,19)
|
0.05 Percent
Standard Deviation 0.10
|
-0.01 Percent
Standard Deviation 0.17
|
-0.02 Percent
Standard Deviation 0.12
|
0.02 Percent
Standard Deviation 0.11
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment. Patients with both baseline and week 36 assessment were included in this analysis.
Reductions in the following measurements were analysed between the baseline visit and the final visit: LA diameter
Outcome measures
| Measure |
Aliskiren
n=12 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=12 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
n=13 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
n=17 Participants
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in Left Ventricular (LV) Function, LA (Left Atrium) Diameter in Combination of Aliskiren With Amlodipine
|
-0.18 mm/m^2
Standard Deviation 1.12
|
-0.07 mm/m^2
Standard Deviation 1.27
|
-0.19 mm/m^2
Standard Deviation 0.96
|
-0.24 mm/m^2
Standard Deviation 1.03
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment. Patients with both baseline and week 36 assessment were included in this analysis.
Reductions in the following measurements were analysed between the baseline visit and the final visit: left atrial volume (biplane Simpson's method)
Outcome measures
| Measure |
Aliskiren
n=6 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=6 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
n=9 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
n=13 Participants
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline in Left Ventricular (LV) Function, Left Atrial Volume (Biplane Simpson's Method) in Combination of Aliskiren With Amlodipine
|
-8.88 cm3/m^2
Standard Deviation 15.74
|
7.78 cm3/m^2
Standard Deviation 17.14
|
-7.42 cm3/m^2
Standard Deviation 24.37
|
1.30 cm3/m^2
Standard Deviation 28.21
|
SECONDARY outcome
Timeframe: Baseline, Week 36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment
Echocardiogram was performed at week 1 and at week 36. Reduction in LVMI is defined as the difference between the LVMI at the final visit and the baseline LVMI
Outcome measures
| Measure |
Aliskiren
n=14 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=15 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
n=16 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
n=20 Participants
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Change From Baseline of LVMI in Combination of Aliskiren With Amlodipine
|
-5.68 g/m2
Standard Deviation 18.95
|
-10.26 g/m2
Standard Deviation 19.40
|
-3.59 g/m2
Standard Deviation 13.46
|
-11.46 g/m2
Standard Deviation 21.71
|
SECONDARY outcome
Timeframe: Baseline, Week 10,18,26,36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment
The mean systolic BP (SBP) and diastolic BP (DBP) readings for the aliskiren and losartan treatment groups, the difference in these values between the two groups and the comparison of post-baseline vs. baseline values
Outcome measures
| Measure |
Aliskiren
n=32 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=37 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Systolic Blood Pressure (SBP)
Baseline, Week 10 (n=30,37)
|
-5.56 mmHg
Standard Deviation 12.89
|
-4.03 mmHg
Standard Deviation 16.93
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Systolic Blood Pressure (SBP)
Baseline, Week 18 (n=29,36)
|
-9.77 mmHg
Standard Deviation 12.25
|
-8.44 mmHg
Standard Deviation 17.30
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Systolic Blood Pressure (SBP)
Baseline, Week 26 (n=29,36)
|
-12.69 mmHg
Standard Deviation 15.05
|
-10.40 mmHg
Standard Deviation 15.74
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Systolic Blood Pressure (SBP)
Baseline, Week 36 (n=32,37)
|
-8.87 mmHg
Standard Deviation 19.26
|
-8.88 mmHg
Standard Deviation 15.91
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 10,18,26,36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment
The mean systolic BP (SBP) and diastolic BP (DBP) readings for the aliskiren and losartan treatment groups, the difference in these values between the two groups and the comparison of post-baseline vs. baseline values
Outcome measures
| Measure |
Aliskiren
n=32 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=37 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Diastolic Blood Pressure (DBP)
Baseline, Week 10 (n=30,37)
|
-1.77 mmHg
Standard Deviation 10.22
|
-3.15 mmHg
Standard Deviation 10.97
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Diastolic Blood Pressure (DBP)
Baseline, Week 18 (n=29,36)
|
-5.34 mmHg
Standard Deviation 10.66
|
-7.07 mmHg
Standard Deviation 9.98
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Diastolic Blood Pressure (DBP)
Baseline, Week 26 (n=29,36)
|
-5.34 mmHg
Standard Deviation 11.37
|
-6.94 mmHg
Standard Deviation 10.10
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Diastolic Blood Pressure (DBP)
Baseline, Week 36 (n=32,37)
|
-4.19 mmHg
Standard Deviation 10.32
|
-6.68 mmHg
Standard Deviation 9.66
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week10,18,26,36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment
Response rate was defined as the proportion of patients with a satisfactory systolic BP response (SBP \< 140 mmHg or reduction of ≥ 10 mmHg compared to baseline) and a satisfactory diastolic BP response (DBP \< 90 mmHg or reduction of ≥ 5 mmHg compared to baseline)
Outcome measures
| Measure |
Aliskiren
n=32 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=37 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Patients With Satisfactory Response Rate
Baseline, Week 10
|
16 Patients
|
15 Patients
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Patients With Satisfactory Response Rate
Baseline, Week 18
|
24 Patients
|
21 Patients
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Patients With Satisfactory Response Rate
Baseline, Week 26
|
24 Patients
|
27 Patients
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Patients With Satisfactory Response Rate
Baseline, Week 36
|
22 Patients
|
25 Patients
|
—
|
—
|
SECONDARY outcome
Timeframe: Week10,18,26,36Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment
The control rate was defined as the proportion of patients with SBP \< 140 mmHg and DBP \< 90 mmHg compared to baseline
Outcome measures
| Measure |
Aliskiren
n=32 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=37 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Patients With SBP < 140 mmHg and DBP < 90 mmHg Compared to Baseline
Control rate at Week 18
|
20 Patients
|
19 Patients
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Patients With SBP < 140 mmHg and DBP < 90 mmHg Compared to Baseline
Control rate at Week 10
|
15 Patients
|
13 Patients
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Patients With SBP < 140 mmHg and DBP < 90 mmHg Compared to Baseline
Control rate at Week 26
|
22 Patients
|
23 Patients
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Patients With SBP < 140 mmHg and DBP < 90 mmHg Compared to Baseline
Control rate at Week 36
|
21 Patients
|
20 Patients
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 10,18,26Population: Intention-to-treat (ITT) population included all patients included in the safety population who had a baseline assessment of the primary variable and at least one post-baseline assessment
The rate of use of first and second antihypertensive rescue drugs added was also assessed at all visits after week 2. The rescue drug at week 10 and 18 for those patients not achieving the required BP was amlodipine, Patients who did not achieve the required BP at week 26 were treated with hydrochlorothiazide
Outcome measures
| Measure |
Aliskiren
n=32 Participants
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Lostaran
n=37 Participants
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
Losartan + Amlodipine
5 mg of amlodipine in addition to the study medication in order to reach the required BP (\<140/90 mmHg). At week 18 the dose of amlodipine can be increased to 10mg if the required level (\<140/90 mmHg) was still not achieved.
|
|---|---|---|---|---|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Rate of Use of Added Antihypertensive Rescue Drugs
Baseline, Week 10 (amlodipine)
|
11 Patients
|
15 Patients
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Rate of Use of Added Antihypertensive Rescue Drugs
Baseline, Week 18 (amlodipine)
|
2 Patients
|
9 Patients
|
—
|
—
|
|
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Rate of Use of Added Antihypertensive Rescue Drugs
Baseline, Week 26 (hydrochlorothiazide)
|
2 Patients
|
4 Patients
|
—
|
—
|
Adverse Events
Aliskiren
Losartan
Serious adverse events
| Measure |
Aliskiren
n=37 participants at risk
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Losartan
n=37 participants at risk
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
|---|---|---|
|
Infections and infestations
Bronchopneumonia
|
2.7%
1/37
|
0.00%
0/37
|
|
Surgical and medical procedures
Coronary artery bypass
|
2.7%
1/37
|
0.00%
0/37
|
Other adverse events
| Measure |
Aliskiren
n=37 participants at risk
Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks
|
Losartan
n=37 participants at risk
Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
|
|---|---|---|
|
Cardiac disorders
Palpitations
|
5.4%
2/37
|
13.5%
5/37
|
|
Gastrointestinal disorders
Abdominal pain
|
5.4%
2/37
|
0.00%
0/37
|
|
Gastrointestinal disorders
Diarrhoea
|
2.7%
1/37
|
5.4%
2/37
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/37
|
5.4%
2/37
|
|
General disorders
Oedema peripheral
|
8.1%
3/37
|
0.00%
0/37
|
|
Infections and infestations
Bronchitis
|
0.00%
0/37
|
5.4%
2/37
|
|
Infections and infestations
Gastroenteritis
|
2.7%
1/37
|
8.1%
3/37
|
|
Infections and infestations
Influenza
|
2.7%
1/37
|
10.8%
4/37
|
|
Infections and infestations
Nasopharyngitis
|
2.7%
1/37
|
8.1%
3/37
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.7%
1/37
|
5.4%
2/37
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.4%
2/37
|
5.4%
2/37
|
|
Nervous system disorders
Dizziness
|
10.8%
4/37
|
8.1%
3/37
|
|
Nervous system disorders
Headache
|
10.8%
4/37
|
16.2%
6/37
|
|
Renal and urinary disorders
Renal colic
|
5.4%
2/37
|
2.7%
1/37
|
|
Vascular disorders
Hypertension
|
5.4%
2/37
|
0.00%
0/37
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
- Publication restrictions are in place
Restriction type: OTHER