Comparison of Amlodipine and Aliskiren in Diabetic Hypertensive Patient With Blood Pressure Not Controlled by Losartan

Comparison Between Amlodipine and Aliskiren in Diabetic Hypertensive Patient With Blood Pressure Not Controlled by Losartan: Effects on Endothelial Function and Renin Concentration and Activity

Assess if aliskiren is capable of enhancing vascular stiffness and endothelial function and compare theses effects and renin activity and concentration to those obtained with a calcium channel blocker, amlodipine, in patients with diabetes mellitus type 2 and blood pressure not controlled by 100 mg per day of losartan.

Study Overview

• Status: Withdrawn
• Conditions: Hypertension; Diabetes Mellitus
• Intervention / Treatment: Drug: Aliskiren; Drug: Amlodipine

Detailed Description

Hypertension and diabetes mellitus are important risk factors for cardiovascular morbidity and mortality. Endothelial dysfunction and vascular rigidity are two pathophysiological mechanisms that may explain this relationship. Recent publications showed that both ACEi (angiotensin converting enzyme inhibitor) and ARB (angiotensin receptor blocker) were capable of improving vascular stiffness and endothelial function, and that these effects occurred despite blood pressure reduction. The major debate that persists is which drug to associate with ACEi or ARB to achieve blood pressure control in diabetic patients. Recent studies showed that even in patients under ACEi or ARB therapy there may be residual activity in the renin-angiotensin-aldosterone system (RASS). Direct renin inhibitors (DRI) are a new class of anti-hypertensive drugs that may complement the blockade of the RASS. Aliskiren was the first drug of this class that completed phase 3 studies and marketed in the 21th century. It's main advantage is that DRI may reduce angiotensin II and aldosterone synthesis without increasing renin levels. This study main objective is to assess if aliskiren is capable of enhancing vascular stiffness and endothelial function and compare theses effects to those obtained with a calcium channel blocker, amlodipine, in patients with diabetes mellitus type 2 and blood pressure not controlled by 100 mg per day of losartan. Vascular stiffness and endothelial function will be measured by: pulse wave velocity, augmentation index, brachial artery flow-mediated vasodilation, peripheral arterial tonometry (EndoPat). Another main objective is to compare plasma renin activity and concentration between those groups.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 20551030
    • Hospital Universitário Pedro Ernesto

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ambulatorial patients with age between 40 and 70 years-old.
• Systemic arterial hypertension previously diagnosed and in use of two or less anti-hypertensive drugs in the preceding 4 weeks.
• Those patients without anti-hypertensive drug prescribed in the last 4 weeks with office systolic blood pressure between 140 and 159 mmHg and diastolic between 90 and 109 mmHg.
• Type 2 diabetes mellitus in use of oral medication that were not changed in the preceding 4 weeks. Glycated hemoglobin A1c less than 9.0%.
• Accepted the consent form.

Exclusion Criteria:

• Office systolic blood pressure equal or more than 180 mmHg, with or without treatment
• Office diastolic blood pressure equal or more than 110 mmHg, with or without treatment
• Evidences of a secondary cause for hypertension
• Glycated hemoglobin A1c > 9.0%
• Insulin therapy
• Chronic kidney disease of level 3 to 5 or in dialysis
• Advanced target organ lesion, obtained by history or additional exams, and defined by: previous myocardial infarction, heart failure with ejection fraction less than 40%, cerebral vascular accident (ischemic or hemorrhagic), peripheral vascular disease (claudication or doppler with obstruction > 50% of vascular lumen), retinopathy with visual loss, symptomatic neuropathy.
• Cardiac arrhythmias, except for ectopic beats
• Any clinical or disabling condition that, in the opinion of the investigators, may confound or prejudice study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aliskiren	Drug: Aliskiren; 300 mg of aliskiren daily for 8 weeks.; Other Names: Rasilez.
Active Comparator: Amlodipine	Drug: Amlodipine; Amlodipine 5 mg daily for 8 weeks.; Other Names: Norvasc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascular stiffness	Vascular stiffness will be measured by pulse wave velocity and augmentation index and compared between anlodipine and aliskiren.	8 weeks
Endothelial function	Access endothelial function by peripheral arterial tonometry and brachial flow-mediated vasodilation and compare it between anlodipine and aliskiren.	8 weeks
Renin activity and concentration	Access plasma renin activity and concentration and compare it between anlodipine and aliskiren.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare drug effects in office blood pressure measurements to those obtained by home blood pressure monitoring and ambulatory blood pressure monitoring	Compare drug effects in office blood pressure measurements to those obtained by home blood pressure monitoring and ambulatory blood pressure monitoring	8 weeks
Assess drugs effects in renin-angiotensin-aldosterone system (RAAS) and correlate it to renin concentration/mass and plasmatic renin activity	Assess drugs effects in RAAS and correlate it to renin concentration/mass and plasmatic renin activity	8 weeks
Correlation of drug effects and uric acid plasmatic concentration	Correlation of drug effects and uric acid plasmatic concentration	8 weeks
Correlation of drug effects and glomerular filtration rate	Correlation of drug effects and glomerular filtration rate	8 weeks
Correlation of drug effects and microalbuminuria	Correlation of drug effects and microalbuminuria	8 weeks
Correlation of drug effects and left ventricular mass and function (systolic and diastolic)	Correlation of drug effects and left ventricular mass and function (systolic and diastolic)	8 weeks

Collaborators and Investigators

• Sponsor: Hospital Universitario Pedro Ernesto
• Collaborators: Novartis
• Investigators: Principal Investigator: Ronaldo A Gismondi, MD, DsC, HUPedroernesto (UERJ); Study Director: Mario F Neves, MD, PhD, HUPedroernesto (UERJ); Study Chair: Wille Oigman, MD, PhD, HUPedroernesto (UERJ)

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Anticipated): April 1, 2013
• Study Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: August 1, 2011
• First Submitted That Met QC Criteria: August 3, 2011
• First Posted (Estimate): August 4, 2011

Study Record Updates

• Last Update Posted (Estimate): March 6, 2012
• Last Update Submitted That Met QC Criteria: March 5, 2012
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Hypertension; Diabetes Mellitus; Endothelial function; Vascular stiffness
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hypertension; Diabetes Mellitus; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Amlodipine
• Other Study ID Numbers: CAALIDH