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

NCT ID: NCT01409408

Last Updated: 2012-03-06

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2013-12-31

Brief Summary

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.

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.

Conditions

Hypertension; Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Aliskiren

Group Type: ACTIVE_COMPARATOR

Aliskiren

Intervention Type: DRUG

300 mg of aliskiren daily for 8 weeks.

Amlodipine

Group Type: ACTIVE_COMPARATOR

Amlodipine

Intervention Type: DRUG

Amlodipine 5 mg daily for 8 weeks.

Interventions

Aliskiren

300 mg of aliskiren daily for 8 weeks.

Intervention Type: DRUG

Amlodipine

Amlodipine 5 mg daily for 8 weeks.

Intervention Type: DRUG

Other Intervention Names

Rasilez.; Norvasc.

Eligibility Criteria

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Hospital Universitario Pedro Ernesto

OTHER

Sponsor Role: lead

Responsible Party

Hospital Universitario Pedro Ernesto

Principal Investigators

Ronaldo A Gismondi, MD, DsC

Role: PRINCIPAL_INVESTIGATOR

HUPedroernesto (UERJ)

Mario F Neves, MD, PhD

Role: STUDY_DIRECTOR

HUPedroernesto (UERJ)

Wille Oigman, MD, PhD

Role: STUDY_CHAIR

HUPedroernesto (UERJ)

Locations

Hospital Universitario Pedro Ernesto

Rio de Janeiro, Rio de Janeiro, Brazil

Countries

Brazil

Other Identifiers

CAALIDH

Identifier Type: -

Identifier Source: org_study_id