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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01176032
First received: August 2, 2010
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Hypertension
Left Ventricle Hypertrophy
Drug: Aliskiren
Drug: Losartan
Drug: Amlodipine
Drug: Hydrochlorothiazide (HCTZ)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The "ALiskiren or Losartan Effects on bioMARKers of Myocardial Remodeling (ALLMARK)" Study

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in C-terminal Propeptide of Procollagen Type I (PICP) [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    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:
  • Change From Baseline in Biomarkers in Heart Disease [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    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 Biomarker Such as Aldosterone (Aldo) in Heart Disease [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    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, LV End-diastolic Volume by Simpson's Rule, and LV End-systolic Volume by Simpson's Rule [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    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 Ejection Fraction (Teicholz), and LV Ejection Fraction (Simpson) [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    Reductions in the following measurements were analysed between the baseline visit and the final visit: LA diameter

  • Change From Baseline in Left Ventricular (LV) Function, Left Atrial Volume (Biplane Simpson's Method) [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    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 Reduction of Left Ventricular Mass Index (LVMI) [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    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 Combination of Aliskiren With Amlodipine in Biomarkers of Heart Disease. [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    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 Biomarker Such as Aldosterone (Aldo) in Heart Disease in Combination of Aliskiren With Amlodipine [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    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 Ejection Fraction (Teicholz), and LV Ejection Fraction (Simpson) in Combination of Aliskiren With Amlodipine [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    Reductions in the following measurements were analysed between the baseline visit and the final visit: LA diameter

  • Change From Baseline in Left Ventricular (LV) Function, Left Atrial Volume (Biplane Simpson's Method) in Combination of Aliskiren With Amlodipine [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 36 ] [ Designated as safety issue: No ]
    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 Systolic Blood Pressure (SBP) [ Time Frame: Baseline, Week 10,18,26,36 ] [ Designated as safety issue: No ]
    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 Reduction in Diastolic Blood Pressure (DBP) [ Time Frame: Baseline, Week 10,18,26,36 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week10,18,26,36 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week10,18,26,36 ] [ Designated as safety issue: No ]
    The control rate was defined as the proportion of patients with SBP < 140 mmHg and DBP < 90 mmHg compared to baseline

  • Effectivness of Aliskiren in Controlling Blood Pressure Compare to Losartan in Terms of Rate of Use of Added Antihypertensive Rescue Drugs [ Time Frame: Baseline, Week 10,18,26 ] [ Designated as safety issue: No ]
    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


Enrollment: 74
Study Start Date: June 2010
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01176032

Locations
Spain
Novartis Investigative Site
Sanlúcar de Barrameda, Andalucia, Spain, 11540
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41009
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site
Utrera, Andalucia, Spain, 41710
Novartis Investigative Site
Burgos, Castilla y Leon, Spain, 09005
Novartis Investigative Site
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
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
Santiago de Compostela, Galicia, Spain, 15706
Novartis Investigative Site
Galdakano, Pais Vasco, Spain, 48960
Novartis Investigative Site
Bilbao, País Vasco, Spain, 48013
Novartis Investigative Site
Vitoria, País Vasco, Spain
Novartis Investigative Site
Barcelona, Spain, 08006
Novartis Investigative Site
Barcelona, Spain, 08025
Novartis Investigative Site
Madrid, Spain, 28046
Novartis Investigative Site
Madrid, Spain, 28035
Novartis Investigative Site
Madrid, Spain, 28040
Novartis Investigative Site
Madrid, Spain, 28009
Novartis Investigative Site
Madrid, Spain, 28041
Novartis Investigative Site
Santander, Spain, 39008
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Chair: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01176032     History of Changes
Other Study ID Numbers: CSPP100AES02, 2009-016735-36
Study First Received: August 2, 2010
Results First Received: April 22, 2014
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration
Spain: Spanish Agency of Medicines

Keywords provided by Novartis:
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
Cardiovascular Diseases
Pathological Conditions, Anatomical
Vascular Diseases
Amlodipine
Hydrochlorothiazide
Losartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Calcium Channel Blockers
Cardiovascular Agents
Diuretics
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 23, 2014