ALiskiren or Losartan Effects on bioMARKers of Myocardial Remodeling

Hypertension Clinical Trial

— ALLMARK  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01176032
• Other study ID #: CSPP100AES02
• Secondary ID: 2009-016735-36
• Status: Completed
• Phase: Phase 4
• First received: August 2, 2010
• Last updated: July 22, 2014
• Start date: June 2010
• Est. completion date: April 2013

Study information

• Verified date: July 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSpain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Hypertrophy
• Left Ventricle Hypertrophy

Intervention

Drug:
• Aliskiren
Aliskiren 300 mg film coated tablets
• Losartan
Losartan 100 mg tablets
• 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.
• Hydrochlorothiazide (HCTZ)
HCTZ 12.5mg was prescribed at visit 5 (week 26) if the required values (<140/90 mmHg) had not been reached.

Locations

Country	Name	City	State
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Bilbao	País Vasco
Spain	Novartis Investigative Site	Burgos	Castilla y Leon
Spain	Novartis Investigative Site	Galdakano	Pais Vasco
Spain	Novartis Investigative Site	Girona	Cataluña
Spain	Novartis Investigative Site	L'Hospitalet de Llobregat	Cataluña
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Sanlúcar de Barrameda	Andalucia
Spain	Novartis Investigative Site	Santa Coloma de Gramanet	Cataluña
Spain	Novartis Investigative Site	Santander
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Torrevieja (Alicante)	Comunidad Valenciana
Spain	Novartis Investigative Site	Utrera	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Vitoria	País Vasco

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No