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

This study has been withdrawn prior to enrollment.
(Due to preliminary results of Altitude Trial.)
Sponsor:
Collaborator:
Novartis
Information provided by:
Hospital Universitario Pedro Ernesto
ClinicalTrials.gov Identifier:
NCT01409408
First received: August 1, 2011
Last updated: March 5, 2012
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Hypertension
Diabetes Mellitus
Drug: Aliskiren
Drug: Amlodipine
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Hospital Universitario Pedro Ernesto:

Primary Outcome Measures:
  • Vascular stiffness [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Vascular stiffness will be measured by pulse wave velocity and augmentation index and compared between anlodipine and aliskiren.

  • Endothelial function [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Access endothelial function by peripheral arterial tonometry and brachial flow-mediated vasodilation and compare it between anlodipine and aliskiren.

  • Renin activity and concentration [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Access plasma renin activity and concentration and compare it between anlodipine and aliskiren.


Secondary Outcome Measures:
  • Compare drug effects in office blood pressure measurements to those obtained by home blood pressure monitoring and ambulatory blood pressure monitoring [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Compare drug effects in office blood pressure measurements to those obtained by home blood pressure monitoring and ambulatory blood pressure monitoring

  • Assess drugs effects in renin-angiotensin-aldosterone system (RAAS) and correlate it to renin concentration/mass and plasmatic renin activity [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Assess drugs effects in RAAS and correlate it to renin concentration/mass and plasmatic renin activity

  • Correlation of drug effects and uric acid plasmatic concentration [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Correlation of drug effects and uric acid plasmatic concentration

  • Correlation of drug effects and glomerular filtration rate [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Correlation of drug effects and glomerular filtration rate

  • Correlation of drug effects and microalbuminuria [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Correlation of drug effects and microalbuminuria

  • Correlation of drug effects and left ventricular mass and function (systolic and diastolic) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Correlation of drug effects and left ventricular mass and function (systolic and diastolic)


Enrollment: 0
Study Start Date: April 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aliskiren Drug: Aliskiren
300 mg of aliskiren daily for 8 weeks.
Other Name: Rasilez.
Active Comparator: Amlodipine Drug: Amlodipine
Amlodipine 5 mg daily for 8 weeks.
Other Name: Norvasc.

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.

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01409408

Locations
Brazil
Hospital Universitario Pedro Ernesto
Rio de Janeiro, Brazil, 20551030
Sponsors and Collaborators
Hospital Universitario Pedro Ernesto
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)
  More Information

No publications provided

Responsible Party: Ronaldo Altenburg Odebrecht Curi Gismondi, Hospital Universitario Pedro Ernesto
ClinicalTrials.gov Identifier: NCT01409408     History of Changes
Other Study ID Numbers: CAALIDH
Study First Received: August 1, 2011
Last Updated: March 5, 2012
Health Authority: Brazil: National Health Surveillance Agency
Brazil: National Committee of Ethics in Research

Keywords provided by Hospital Universitario Pedro Ernesto:
Hypertension
Diabetes Mellitus
Vascular stiffness
Endothelial function

Additional relevant MeSH terms:
Diabetes Mellitus
Hypertension
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vascular Diseases
Cardiovascular Diseases
Amlodipine
Losartan
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Antihypertensive Agents
Anti-Arrhythmia Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on July 28, 2014