ALLMARK: ALiskiren or Losartan Effects on bioMARKers of Myocardial Remodeling

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01176032
• Collaborator: (none)
• Enrollment: 74
• Locations: 25
• Arms: 2
• Duration (Months): 34
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess efficacy of aliskiren for reducing circulating levels of biomarkers of left ventricular (LV) remodeling associated with LV hypertrophy (LVH) in hypertensive patients.

Condition or Disease	Intervention/Treatment	Phase
Hypertension; Left Ventricle Hypertrophy	Drug: Aliskiren; Drug: Losartan; Drug: Amlodipine; Drug: Hydrochlorothiazide (HCTZ)	Phase 4

Detailed Description

Blood pressure was measured 10 weeks after starting treatment (visit 3). All patients who did not achieve the required blood pressure (<140/90 mmHg) after 8 weeks of treatment at the maximum doses of study medication were given 5 mg of amlodipine in addition to the study medication in order to reach the required BP (<140/90 mmHg).

The patient's blood pressure was assessed at visit 4 (week 18) and if it was still not at the required level (<140/90 mmHg), the dose of amlodipine was increased to 10 mg.

Blood pressure was again assessed at visit 5 (week 26) and if the required values had not been reached (<140/90 mmHg), a 12.5 mg dose of hydrochlorothiazide (HCTZ) was prescribed

Study Design

• Study Type: Interventional
• Actual Enrollment: 74 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The "ALiskiren or Losartan Effects on bioMARKers of Myocardial Remodeling (ALLMARK)" Study
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aliskiren Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks. In addition to the study medication, amlodipine 5mg was given to patients who did not achieve the required blood pressure (<140/90 mmHg) after 8 weeks of treatment at the maximum doses of study medication. At week 18 the dose of amlodipine was increased to 10mg if the required level (<140/90 mmHg) was still not achieved. HCTZ 12.5mg was prescribed at week 26 if the required values (<140/90 mmHg) had not been reached.	Drug: Aliskiren; Aliskiren 300 mg film coated tablets; Other Names: Rasilez ; Drug: Amlodipine; Amlodipine 5mg was given to patients who did not achieve the required blood pressure (<140/90 mmHg) after 8 weeks (visit 3)of treatment at the maximum doses of study medication in addition to the study medication in order to reach the required BP. at visit 4 (week 18) the dose of amlodipine was increased to 10mg if the required level (<140/90 mmHg) was still not achieved.; Drug: Hydrochlorothiazide (HCTZ); HCTZ 12.5mg was prescribed at visit 5 (week 26) if the required values (<140/90 mmHg) had not been reached.
Active Comparator: Lostaran Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks. In addition to the study medication, amlodipine 5mg was given to patients who did not achieve the required blood pressure (<140/90 mmHg) after 8 weeks of treatment at the maximum doses of study medication. At week 18 the dose of amlodipine was increased to 10mg if the required level (<140/90 mmHg) was still not achieved. HCTZ 12.5mg was prescribed at week 26 if the required values (<140/90 mmHg) had not been reached.	Drug: Losartan; Losartan 100 mg tablets; Drug: Amlodipine; Amlodipine 5mg was given to patients who did not achieve the required blood pressure (<140/90 mmHg) after 8 weeks (visit 3)of treatment at the maximum doses of study medication in addition to the study medication in order to reach the required BP. at visit 4 (week 18) the dose of amlodipine was increased to 10mg if the required level (<140/90 mmHg) was still not achieved.; Drug: Hydrochlorothiazide (HCTZ); HCTZ 12.5mg was prescribed at visit 5 (week 26) if the required values (<140/90 mmHg) had not been reached.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in C-terminal Propeptide of Procollagen Type I (PICP) [Baseline, Week 36]

   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.

Secondary Outcome Measures

1. Change From Baseline in Biomarkers in Heart Disease [Baseline, Week 36]

   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)

2. Change From Baseline in Biomarker Such as Aldosterone (Aldo) in Heart Disease [Baseline, Week 36]

   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)

3. 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 [Baseline, Week 36]

   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

4. Change From Baseline in Left Ventricular (LV) Function, LV Ejection Fraction (Teicholz), and LV Ejection Fraction (Simpson) [Baseline, Week 36]

   Reductions in the following measurements were analysed between the baseline visit and the final visit: LV ejection fraction (Teicholz), and LV ejection fraction (Simpson)

5. Change From Baseline in Left Ventricular (LV) Function, LA (Left Atrium) Diameter [Baseline, Week 36]

   Reductions in the following measurements were analysed between the baseline visit and the final visit: LA diameter

6. Change From Baseline in Left Ventricular (LV) Function, Left Atrial Volume (Biplane Simpson's Method) [Baseline, Week 36]

   Reductions in the following measurements were analysed between the baseline visit and the final visit: left atrial volume (biplane Simpson's method)

7. Change From Baseline in Reduction of Left Ventricular Mass Index (LVMI) [Baseline, Week 36]

   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

8. Change From Baseline in Combination of Aliskiren With Amlodipine in Biomarkers of Heart Disease. [Baseline, Week 36]

   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)

9. Change From Baseline in Biomarker Such as Aldosterone (Aldo) in Heart Disease in Combination of Aliskiren With Amlodipine [Baseline, Week 36]

   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).

10. 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 [Baseline, Week 36]

    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

11. Change From Baseline in Left Ventricular (LV) Function, LV Ejection Fraction (Teicholz), and LV Ejection Fraction (Simpson) in Combination of Aliskiren With Amlodipine [Baseline, Week 36]

    Reductions in the following measurements were analysed between the baseline visit and the final visit: LV ejection fraction (Teicholz), and LV ejection fraction (Simpson)

12. Change From Baseline in Left Ventricular (LV) Function, LA (Left Atrium) Diameter in Combination of Aliskiren With Amlodipine [Baseline, Week 36]

    Reductions in the following measurements were analysed between the baseline visit and the final visit: LA diameter

13. Change From Baseline in Left Ventricular (LV) Function, Left Atrial Volume (Biplane Simpson's Method) in Combination of Aliskiren With Amlodipine [Baseline, Week 36]

    Reductions in the following measurements were analysed between the baseline visit and the final visit: left atrial volume (biplane Simpson's method)

14. Change From Baseline of LVMI in Combination of Aliskiren With Amlodipine [Baseline, Week 36]

    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

15. Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Systolic Blood Pressure (SBP) [Baseline, Week 10,18,26,36]

    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

16. Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Diastolic Blood Pressure (DBP) [Baseline, Week 10,18,26,36]

    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

17. Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Patients With Satisfactory Response Rate [Baseline, Week10,18,26,36]

    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)

18. 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 [Week10,18,26,36]

    The control rate was defined as the proportion of patients with SBP < 140 mmHg and DBP < 90 mmHg compared to baseline

19. Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Rate of Use of Added Antihypertensive Rescue Drugs [Baseline, Week 10,18,26]

    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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient with hypertension

• Confirmed concentric left ventricular hypertrophy:

• LVMI > 49.2 g/m2.7 for men and >46.7 g/m2.7 for women

• Relative wall thickness > 0.42

Exclusion Criteria:

• Sever or secondary HTN

• LV ejection fraction of <40%

• Patient with compelling indication to ACEIs or ARBs or BB

• History of myocardial infarction, coronary artery bypass surgery, PTC intervention, TIA or stroke within 6 months of study entry

• History of collagenopathies, osteopathy

• eGFR <30 ml/min/1,73 m2, serum potassium ≥5,2 mEq/L

• Morbid obesity (BMI ≥ 42 kg/m2

• Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Sanlúcar de Barrameda	Andalucia	Spain	11540
2	Novartis Investigative Site	Sevilla	Andalucia	Spain	41009
3	Novartis Investigative Site	Sevilla	Andalucia	Spain	41013
4	Novartis Investigative Site	Utrera	Andalucia	Spain	41710
5	Novartis Investigative Site	Burgos	Castilla y Leon	Spain	09005
6	Novartis Investigative Site	Barcelona	Cataluña	Spain	08036
7	Novartis Investigative Site	Girona	Cataluña	Spain	17007
8	Novartis Investigative Site	L'Hospitalet de Llobregat	Cataluña	Spain	08907
9	Novartis Investigative Site	Santa Coloma de Gramanet	Cataluña	Spain
10	Novartis Investigative Site	Alicante	Comunidad Valenciana	Spain	03004
11	Novartis Investigative Site	Torrevieja (Alicante)	Comunidad Valenciana	Spain	03186
12	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46010
13	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46014
14	Novartis Investigative Site	Santiago de Compostela	Galicia	Spain	15706
15	Novartis Investigative Site	Galdakano	Pais Vasco	Spain	48960
16	Novartis Investigative Site	Bilbao	País Vasco	Spain	48013
17	Novartis Investigative Site	Vitoria	País Vasco	Spain
18	Novartis Investigative Site	Barcelona		Spain	08006
19	Novartis Investigative Site	Barcelona		Spain	08025
20	Novartis Investigative Site	Madrid		Spain	28009
21	Novartis Investigative Site	Madrid		Spain	28035
22	Novartis Investigative Site	Madrid		Spain	28040
23	Novartis Investigative Site	Madrid		Spain	28041
24	Novartis Investigative Site	Madrid		Spain	28046
25	Novartis Investigative Site	Santander		Spain	39008

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
• Study Chair: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01176032
• Other Study ID Numbers: CSPP100AES02; 2009-016735-36
• First Posted: Aug 5, 2010
• Last Update Posted: Jul 24, 2014
• Last Verified: Jul 1, 2014

• Keywords provided by Novartis Pharmaceuticals: Aliskiren; hypertension; concentric LVH; LV remodeling; LVMI; biomarkers; PICP; CT-1; MMP-1; TIMP-1; AnxA5; Aldosterone; Essential hypertension with concentric left ventricle hypertrophy
• Additional relevant MeSH terms: Hypertension; Hypertrophy; Losartan; Amlodipine; Hydrochlorothiazide

Study Results

Participant Flow

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Period Title: Overall Study
STARTED	37	37
Intention-to-treat (ITT) Population	32	37
COMPLETED	31	36
NOT COMPLETED	6	1

Baseline Characteristics

Arm/Group Title	Aliskiren	Lostaran	Total
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks	Total of all reporting groups
Overall Participants	32	37	69
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.34 (9.34)	58.05 (10.34)	59.12 (9.88)
Sex: Female, Male (Count of Participants)
Female	9 28.1%	11 29.7%	20 29%
Male	23 71.9%	26 70.3%	49 71%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in C-terminal Propeptide of Procollagen Type I (PICP)
Description	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.
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Measure Participants	32	37
Mean (Standard Deviation) [ug/l]	-5.22 (20.37)	-4.25 (24.80)

2. Secondary Outcome

Title	Change From Baseline in Biomarkers in Heart Disease
Description	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)
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Measure Participants	32	37
cardiotrophin-1 (CT-1) (n=32,37)	-169.15 (561.51)	-128.23 (568.02)
matrix metalloproteinase-1 (MMP-1) (n=32,37)	5.93 (13.33)	5.51 (9.58)
tissue inhibitor of MMPs (TIMP-1) (n=32,37)	-0.70 (59.18)	9.15 (42.58)
annexin A5 (AnxA5) (n=31,37)	-0.98 (7.33)	-1.21 (4.75)
NT-proBNP (n=31,34)	18.66 (165.21)	-7.55 (38.11)

3. Secondary Outcome

Title	Change From Baseline in Biomarker Such as Aldosterone (Aldo) in Heart Disease
Description	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)
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Measure Participants	32	37
Mean (Standard Deviation) [ng/dl]	-1.81 (27.78)	-7.90 (76.35)

4. Secondary Outcome

Title	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
Description	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
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Measure Participants	32	37
LV end-diastolic volume (n=22,34)	2.30 (35.65)	0.54 (33.19)
LV end-systolic volume (n=22,34)	-0.92 (12.24)	0.64 (21.01)

5. Secondary Outcome

Title	Change From Baseline in Left Ventricular (LV) Function, LV Ejection Fraction (Teicholz), and LV Ejection Fraction (Simpson)
Description	Reductions in the following measurements were analysed between the baseline visit and the final visit: LV ejection fraction (Teicholz), and LV ejection fraction (Simpson)
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Measure Participants	32	37
LV ejection fraction Teicholz(n=29,36)	0.00 (0.11)	0.01 (0.08)
LV ejection fraction Simpson(n=22,34)	0.02 (0.14)	0.00 (0.11)

6. Secondary Outcome

Title	Change From Baseline in Left Ventricular (LV) Function, LA (Left Atrium) Diameter
Description	Reductions in the following measurements were analysed between the baseline visit and the final visit: LA diameter
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Measure Participants	24	30
Mean (Standard Deviation) [mm/m^2]	-0.13 (1.17)	-0.22 (0.98)

7. Secondary Outcome

Title	Change From Baseline in Left Ventricular (LV) Function, Left Atrial Volume (Biplane Simpson's Method)
Description	Reductions in the following measurements were analysed between the baseline visit and the final visit: left atrial volume (biplane Simpson's method)
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Measure Participants	12	22
Mean (Standard Deviation) [cm3/m^2]	-0.55 (17.94)	-2.27 (26.46)

8. Secondary Outcome

Title	Change From Baseline in Reduction of Left Ventricular Mass Index (LVMI)
Description	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
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Measure Participants	32	37
Mean (Standard Deviation) [g/m^2]	-8.05 (18.98)	-7.96 (18.69)

9. Secondary Outcome

Title	Change From Baseline in Combination of Aliskiren With Amlodipine in Biomarkers of Heart Disease.
Description	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)
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aliskiren	Aliskiren + Amlodipine	Losartan	Losartan + Amlodipine
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	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.	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks	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.
Measure Participants	15	17	16	21
CT-1(n=15,17,16,21)	-289.18 (608.91)	-63.23 (510.91)	156.89 (599.29)	-345.47 (443.63)
ANXA5 (n=15,16,16,21)	-1.24 (3.70)	-0.74 (9.73)	-1.73 (4.21)	-0.81 (5.20)
MMP-1(n=15,17,16,21)	7.00 (10.28)	4.99 (15.80)	5.47 (7.88)	5.54 (10.89)
TIMP-1 (n=15,17,16,21)	-10.01 (73.00)	7.51 (44.38)	21.38 (38.40)	-0.16 (44.13)
NT-proBNP (n=15,16,15,19)	21.00 (214.06)	16.46 (108.69)	-3.68 (23.78)	-10.60 (46.91)

10. Secondary Outcome

Title	Change From Baseline in Biomarker Such as Aldosterone (Aldo) in Heart Disease in Combination of Aliskiren With Amlodipine
Description	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).
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aliskiren	Aliskiren + Amlodipine	Losartan	Losartan + Amlodipine
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	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.	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks	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.
Measure Participants	15	17	16	21
Mean (Standard Deviation) [ng/dl]	2.81 (21.36)	-5.89 (32.54)	-3.12 (32.45)	-11.55 (98.35)

11. Secondary Outcome

Title	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
Description	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
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aliskiren	Aliskiren + Amlodipinet	Losartan	Losartan + Amlodipine
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	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.	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks	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.
Measure Participants	15	17	16	21
LV end-diastolic volume (n=11,11,15,19)	6.60 (40.43)	-2.00 (31.51)	5.01 (38.15)	-2.98 (29.30)
LV end-systolic volume (n=11,11, 15,19)	-2.93 (13.24)	1.09 (11.44)	6.11 (23.82)	-3.69 (17.97)

12. Secondary Outcome

Title	Change From Baseline in Left Ventricular (LV) Function, LV Ejection Fraction (Teicholz), and LV Ejection Fraction (Simpson) in Combination of Aliskiren With Amlodipine
Description	Reductions in the following measurements were analysed between the baseline visit and the final visit: LV ejection fraction (Teicholz), and LV ejection fraction (Simpson)
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aliskiren	Aliskiren + Amlodipinet	Losartan	Losartan + Amlodipine
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	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.	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks	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.
Measure Participants	15	17	16	21
LV ejection fraction Teicholz (n=14,15,16,20)	0.00 (0.09)	-0.00 (0.13)	-0.00 (0.07)	0.01 (0.09)
LV ejection fraction Simpson(n=11,11,15,19)	0.05 (0.10)	-0.01 (0.17)	-0.02 (0.12)	0.02 (0.11)

13. Secondary Outcome

Title	Change From Baseline in Left Ventricular (LV) Function, LA (Left Atrium) Diameter in Combination of Aliskiren With Amlodipine
Description	Reductions in the following measurements were analysed between the baseline visit and the final visit: LA diameter
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aliskiren	Aliskiren + Amlodipinet	Losartan	Losartan + Amlodipine
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	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.	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks	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.
Measure Participants	12	12	13	17
Mean (Standard Deviation) [mm/m^2]	-0.18 (1.12)	-0.07 (1.27)	-0.19 (0.96)	-0.24 (1.03)

14. Secondary Outcome

Title	Change From Baseline in Left Ventricular (LV) Function, Left Atrial Volume (Biplane Simpson's Method) in Combination of Aliskiren With Amlodipine
Description	Reductions in the following measurements were analysed between the baseline visit and the final visit: left atrial volume (biplane Simpson's method)
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aliskiren	Aliskiren + Amlodipinet	Losartan	Losartan + Amlodipine
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	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.	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks	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.
Measure Participants	6	6	9	13
Mean (Standard Deviation) [cm3/m^2]	-8.88 (15.74)	7.78 (17.14)	-7.42 (24.37)	1.30 (28.21)

15. Secondary Outcome

Title	Change From Baseline of LVMI in Combination of Aliskiren With Amlodipine
Description	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
Time Frame	Baseline, Week 36

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aliskiren	Aliskiren + Amlodipinet	Losartan	Losartan + Amlodipine
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	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.	losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks	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.
Measure Participants	14	15	16	20
Mean (Standard Deviation) [g/m2]	-5.68 (18.95)	-10.26 (19.40)	-3.59 (13.46)	-11.46 (21.71)

16. Secondary Outcome

Title	Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Systolic Blood Pressure (SBP)
Description	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
Time Frame	Baseline, Week 10,18,26,36

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Measure Participants	32	37
Baseline, Week 10 (n=30,37)	-5.56 (12.89)	-4.03 (16.93)
Baseline, Week 18 (n=29,36)	-9.77 (12.25)	-8.44 (17.30)
Baseline, Week 26 (n=29,36)	-12.69 (15.05)	-10.40 (15.74)
Baseline, Week 36 (n=32,37)	-8.87 (19.26)	-8.88 (15.91)

17. Secondary Outcome

Title	Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Diastolic Blood Pressure (DBP)
Description	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
Time Frame	Baseline, Week 10,18,26,36

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Measure Participants	32	37
Baseline, Week 10 (n=30,37)	-1.77 (10.22)	-3.15 (10.97)
Baseline, Week 18 (n=29,36)	-5.34 (10.66)	-7.07 (9.98)
Baseline, Week 26 (n=29,36)	-5.34 (11.37)	-6.94 (10.10)
Baseline, Week 36 (n=32,37)	-4.19 (10.32)	-6.68 (9.66)

18. Secondary Outcome

Title	Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Patients With Satisfactory Response Rate
Description	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)
Time Frame	Baseline, Week10,18,26,36

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Measure Participants	32	37
Baseline, Week 10	16	15
Baseline, Week 18	24	21
Baseline, Week 26	24	27
Baseline, Week 36	22	25

19. Secondary Outcome

Title	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
Description	The control rate was defined as the proportion of patients with SBP < 140 mmHg and DBP < 90 mmHg compared to baseline
Time Frame	Week10,18,26,36

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Measure Participants	32	37
Control rate at Week 10	15	13
Control rate at Week 18	20	19
Control rate at Week 26	22	23
Control rate at Week 36	21	20

20. Secondary Outcome

Title	Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Rate of Use of Added Antihypertensive Rescue Drugs
Description	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
Time Frame	Baseline, Week 10,18,26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aliskiren	Lostaran
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks	Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
Measure Participants	32	37
Baseline, Week 10 (amlodipine)	11	15
Baseline, Week 18 (amlodipine)	2	9
Baseline, Week 26 (hydrochlorothiazide)	2	4

Adverse Events

Arm/Group Title	Aliskiren		Losartan
Arm/Group Description	Aliskiren 150 mg od for 2 weeks and up-titration to aliskiren 300 mg od for 34 weeks		Losartan 50 mg od for 2 weeks and up-titration to losartan 100 mg od for 34 weeks
All Cause Mortality
	Aliskiren		Losartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aliskiren		Losartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/37 (5.4%)		0/37 (0%)
Infections and infestations
Bronchopneumonia	1/37 (2.7%)		0/37 (0%)
Surgical and medical procedures
Coronary artery bypass	1/37 (2.7%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	Aliskiren		Losartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/37 (32.4%)		16/37 (43.2%)
Cardiac disorders
Palpitations	2/37 (5.4%)		5/37 (13.5%)
Gastrointestinal disorders
Abdominal pain	2/37 (5.4%)		0/37 (0%)
Diarrhoea	1/37 (2.7%)		2/37 (5.4%)
Vomiting	0/37 (0%)		2/37 (5.4%)
General disorders
Oedema peripheral	3/37 (8.1%)		0/37 (0%)
Infections and infestations
Bronchitis	0/37 (0%)		2/37 (5.4%)
Gastroenteritis	1/37 (2.7%)		3/37 (8.1%)
Influenza	1/37 (2.7%)		4/37 (10.8%)
Nasopharyngitis	1/37 (2.7%)		3/37 (8.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/37 (2.7%)		2/37 (5.4%)
Back pain	2/37 (5.4%)		2/37 (5.4%)
Nervous system disorders
Dizziness	4/37 (10.8%)		3/37 (8.1%)
Headache	4/37 (10.8%)		6/37 (16.2%)
Renal and urinary disorders
Renal colic	2/37 (5.4%)		1/37 (2.7%)
Vascular disorders
Hypertension	2/37 (5.4%)		0/37 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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