ALiskiren or Losartan Effects on bioMARKers of Myocardial Remodeling
- Conditions
- HypertensionLeft Ventricle Hypertrophy
- Interventions
- Registration Number
- NCT01176032
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 74
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Aliskiren Hydrochlorothiazide (HCTZ) 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. Lostaran Hydrochlorothiazide (HCTZ) 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. Aliskiren 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. Aliskiren Amlodipine 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. Lostaran Losartan 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. Lostaran Amlodipine 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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)
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
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).
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
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
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)
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)
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)
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
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
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
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)
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)
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
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)
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
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
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)
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
Trial Locations
- Locations (1)
Novartis Investigative Site
🇪🇸Santander, Spain