ALiskiren or Losartan Effects on bioMARKers of Myocardial Remodeling (ALLMARK)

The "ALiskiren or Losartan Effects on bioMARKers of Myocardial Remodeling (ALLMARK)" Study

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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Left Ventricle Hypertrophy
• Intervention / Treatment: Drug: Aliskiren; Drug: Amlodipine; Drug: Hydrochlorothiazide (HCTZ); Drug: Losartan

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 Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08025
    • Novartis Investigative Site
  • Barcelona, Spain, 08006
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Madrid, Spain, 28035
    • Novartis Investigative Site
  • Santander, Spain, 39008
    • Novartis Investigative Site
  • Andalucia
    • Sanlúcar de Barrameda, Andalucia, Spain, 11540
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41009
      • Novartis Investigative Site
    • Utrera, Andalucia, Spain, 41710
      • Novartis Investigative Site
  • Castilla y Leon
    • Burgos, Castilla y Leon, Spain, 09005
      • Novartis Investigative Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08036
      • Novartis Investigative Site
    • Girona, Cataluña, Spain, 17007
      • Novartis Investigative Site
    • L'Hospitalet de Llobregat, Cataluña, Spain, 08907
      • Novartis Investigative Site
    • Santa Coloma de Gramanet, Cataluña, Spain
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Alicante, Comunidad Valenciana, Spain, 03004
      • Novartis Investigative Site
    • Torrevieja (Alicante), Comunidad Valenciana, Spain, 03186
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46014
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
  • Pais Vasco
    • Galdakano, Pais Vasco, Spain, 48960
      • Novartis Investigative Site
  • País Vasco
    • Bilbao, País Vasco, Spain, 48013
      • Novartis Investigative Site
    • Vitoria, País Vasco, Spain
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: 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.; Drug: Losartan; Losartan 100 mg tablets

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Biomarkers in Heart Disease	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)	Baseline, Week 36
Change From Baseline in Biomarker Such as Aldosterone (Aldo) in Heart Disease	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)	Baseline, Week 36
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	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	Baseline, Week 36
Change From Baseline in Left Ventricular (LV) Function, LV Ejection Fraction (Teicholz), and LV Ejection Fraction (Simpson)	Reductions in the following measurements were analysed between the baseline visit and the final visit: LV ejection fraction (Teicholz), and LV ejection fraction (Simpson)	Baseline, Week 36
Change From Baseline in Left Ventricular (LV) Function, LA (Left Atrium) Diameter	Reductions in the following measurements were analysed between the baseline visit and the final visit: LA diameter	Baseline, Week 36
Change From Baseline in Left Ventricular (LV) Function, Left Atrial Volume (Biplane Simpson's Method)	Reductions in the following measurements were analysed between the baseline visit and the final visit: left atrial volume (biplane Simpson's method)	Baseline, Week 36
Change From Baseline in Reduction of Left Ventricular Mass Index (LVMI)	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	Baseline, Week 36
Change From Baseline in Combination of Aliskiren With Amlodipine in Biomarkers of Heart Disease.	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)	Baseline, Week 36
Change From Baseline in Biomarker Such as Aldosterone (Aldo) in Heart Disease in Combination of Aliskiren With Amlodipine	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).	Baseline, Week 36
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	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	Baseline, Week 36
Change From Baseline in Left Ventricular (LV) Function, LV Ejection Fraction (Teicholz), and LV Ejection Fraction (Simpson) in Combination of Aliskiren With Amlodipine	Reductions in the following measurements were analysed between the baseline visit and the final visit: LV ejection fraction (Teicholz), and LV ejection fraction (Simpson)	Baseline, Week 36
Change From Baseline in Left Ventricular (LV) Function, LA (Left Atrium) Diameter in Combination of Aliskiren With Amlodipine	Reductions in the following measurements were analysed between the baseline visit and the final visit: LA diameter	Baseline, Week 36
Change From Baseline in Left Ventricular (LV) Function, Left Atrial Volume (Biplane Simpson's Method) in Combination of Aliskiren With Amlodipine	Reductions in the following measurements were analysed between the baseline visit and the final visit: left atrial volume (biplane Simpson's method)	Baseline, Week 36
Change From Baseline of LVMI in Combination of Aliskiren With Amlodipine	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	Baseline, Week 36
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Systolic Blood Pressure (SBP)	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	Baseline, Week 10,18,26,36
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Reduction in Diastolic Blood Pressure (DBP)	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	Baseline, Week 10,18,26,36
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Patients With Satisfactory Response Rate	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)	Baseline, Week10,18,26,36
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	The control rate was defined as the proportion of patients with SBP < 140 mmHg and DBP < 90 mmHg compared to baseline	Week10,18,26,36
Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Rate of Use of Added Antihypertensive Rescue Drugs	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	Baseline, Week 10,18,26

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: August 2, 2010
• First Submitted That Met QC Criteria: August 3, 2010
• First Posted (Estimate): August 5, 2010

Study Record Updates

• Last Update Posted (Estimate): July 24, 2014
• Last Update Submitted That Met QC Criteria: July 22, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: biomarkers; hypertension; Aliskiren; Aldosterone; MMP-1; TIMP-1; LV remodeling; LVMI; CT-1; concentric LVH; PICP; AnxA5; Essential hypertension with concentric left ventricle hypertrophy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Hypertension; Hypertrophy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Amlodipine; Losartan; Hydrochlorothiazide
• Other Study ID Numbers: CSPP100AES02; 2009-016735-36 (EudraCT Number)