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

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01409408
• Other study ID #: CAALIDH
• Status: Withdrawn
• Phase: Phase 4
• First received: August 1, 2011
• Last updated: March 5, 2012
• Start date: April 2011
• Est. completion date: December 2013

Study information

• Verified date: April 2011
• Source: Hospital Universitario Pedro Ernesto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Health Surveillance AgencyBrazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Hypertension

Intervention

Drug:
• Aliskiren
300 mg of aliskiren daily for 8 weeks.
• Amlodipine
Amlodipine 5 mg daily for 8 weeks.

Locations

Country	Name	City	State
Brazil	Hospital Universitario Pedro Ernesto	Rio de Janeiro

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Universitario Pedro Ernesto	Novartis

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vascular stiffness	Vascular stiffness will be measured by pulse wave velocity and augmentation index and compared between anlodipine and aliskiren.	8 weeks	No
Primary	Endothelial function	Access endothelial function by peripheral arterial tonometry and brachial flow-mediated vasodilation and compare it between anlodipine and aliskiren.	8 weeks	No
Primary	Renin activity and concentration	Access plasma renin activity and concentration and compare it between anlodipine and aliskiren.	8 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	Correlation of drug effects and uric acid plasmatic concentration	Correlation of drug effects and uric acid plasmatic concentration	8 weeks	No
Secondary	Correlation of drug effects and glomerular filtration rate	Correlation of drug effects and glomerular filtration rate	8 weeks	No
Secondary	Correlation of drug effects and microalbuminuria	Correlation of drug effects and microalbuminuria	8 weeks	No
Secondary	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	No