Imidapril and Candesartan on Fibrinolysis and Insulin-Sensitivity in Patients With Mild to Moderate Hypertension
Primary Purpose
Essential Hypertension
Status
Unknown status
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Imidapril
Candesartan
Sponsored by
About this trial
This is an interventional treatment trial for Essential Hypertension focused on measuring Hypertension, Insulin sensitivity, Fibrinolysis
Eligibility Criteria
Inclusion Criteria:
- Age 18-65 years
- DBP ≥ 90 < 110 mmHg and SBP ≥ 140 < 180 mmHg
- Normal Body Mass Index (BMI) (≤ 25 Kg/m2)
- Normal kidney function (Creatinine Clearance > 80 ml/min)
- Normocholesterolemia (TC < 250 mg/dl)
At least one of the following risk factor:
- age (M > 55 years)
- smoking
- family history of premature CV disease
- echocardiographic LVH
- carotid wall thickening (IMT > 0.9 mm)
- ankle/brachial BP < 0.9
Exclusion Criteria:
- Secondary hypertension
- Overweight or obese state (BMI ≥ 25 Kg/m2)
- Suspected history of allergy to the ARBs, or ACEs
- Malignancy
- Renal, hepatic, endocrine, or gastrointestinal disease
- Women who are pregnant and lactating
- Women child-bearing potential
- Heart failure
- AMI and/or stroke in the previous 6 months
- CHD
- Diabetes mellitus
Sites / Locations
- University of PaviaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
2
1
Arm Description
Imidapril
Candesartan
Outcomes
Primary Outcome Measures
PAI-1 level and t-PA activity time course changes
t-PA activity at the desmopressin test
Insulin sensitivity state through euglycemic hyperinsulinemic clamp method
Secondary Outcome Measures
Blood pressure changes
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00644475
Brief Title
Imidapril and Candesartan on Fibrinolysis and Insulin-Sensitivity in Patients With Mild to Moderate Hypertension
Official Title
Randomized, Controlled, Parallel Arm, PROBE Study to Evaluate Different Effects of Imidapril and Candesartan on Fibrinolysis and Insulin-Sensitivity in Patients With Mild to Moderate Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
March 2008
Overall Recruitment Status
Unknown status
Study Start Date
March 2008 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
March 2009 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
University of Pavia
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
BACKGROUND The effects of ACE-inhibitors on fibrinolysis are well documented. Experimental and clinical studies have shown that ACE inhibitors induce a reduction in plasma PAI-1 levels in many cardiovascular diseases, like hypertension, coronary heart disease, and heart failure. Their effects on t-PA are more controversial, due to the fact that t-PA exists in several forms, including free and bound to PAI-1. Indeed an increase in t-PA activity has been observed in humans and it seems related to bradykinin increase which is known to stimulate endothelial t-PA synthesis. These favourable effects on fibrinolysis could be related not only to the Angiotensin II reduction and the bradykinin increase but also to the improvement in insulin sensitivity, as insulin has been suggested as one of the main regulators of fibrinolytic activity.
To date conflicting results have been reported about the effects of ARBs on fibrinolysis. Some studies have reported small improvements, others no significant effect. These conflicting results may be due to possible methodological bias but a possible pathophysiological explanation might be that receptor subtypes other than AT1 mediate the effect of Angiotensin-II on endothelial PAI-1 expression, i.e. the AT4 receptors, and during AT1 receptor blockade there is an important increase not only of Angiotensin-II, but also of all its catabolites including Angiotensin IV. The dissimilar effects on of ACE Is and ARBs may also depend on their different action on the RAS and their different effect on insulin sensitivity: ACE-Is improve insulin sensitivity, while the majority of ARBs have been reported to have a neutral effect. Moreover, unlike ACE-Is, ARBs do not affect the metabolism of bradykinin, which is known to stimulate t-PA synthesis and release.
AIM OF THE STUDY The aim of this study is to verify the effect of imidapril compared to candesartan on insulin sensitivity, evaluated through the euglycemic hyperinsulinemic clamp, and on fibrinolysis, evaluated through the plasma PAI-1 and t-PA activity, in mild to moderate hypertensive patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Essential Hypertension
Keywords
Hypertension, Insulin sensitivity, Fibrinolysis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
2
Arm Type
Experimental
Arm Description
Imidapril
Arm Title
1
Arm Type
Active Comparator
Arm Description
Candesartan
Intervention Type
Drug
Intervention Name(s)
Imidapril
Other Intervention Name(s)
Not yet registered in Italy
Intervention Description
tablets; 5, 10, 15, 20 mg; od; 12 weeks
Intervention Type
Drug
Intervention Name(s)
Candesartan
Other Intervention Name(s)
Registered in Italy
Intervention Description
tablets; 8, 16, 24, and 32 mg; od; 12 weeks
Primary Outcome Measure Information:
Title
PAI-1 level and t-PA activity time course changes
Time Frame
Desmopressin and Clamp venous blood samples will be taken for all patients between 08.00 and 09.00 at 0 and 12 weeks; week 0, 1, 2, 4, 8, and 12 for the others
Title
t-PA activity at the desmopressin test
Time Frame
Desmopressin and Clamp venous blood samples will be taken for all patients between 08.00 and 09.00 at 0 and 12 weeks; week 0, 1, 2, 4, 8, and 12 for the others
Title
Insulin sensitivity state through euglycemic hyperinsulinemic clamp method
Time Frame
Desmopressin and Clamp venous blood samples will be taken for all patients between 08.00 and 09.00 at 0 and 12 weeks; week 0, 1, 2, 4, 8, and 12 for the others
Secondary Outcome Measure Information:
Title
Blood pressure changes
Time Frame
At 0, 1, 2, 4, 8, and 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18-65 years
DBP ≥ 90 < 110 mmHg and SBP ≥ 140 < 180 mmHg
Normal Body Mass Index (BMI) (≤ 25 Kg/m2)
Normal kidney function (Creatinine Clearance > 80 ml/min)
Normocholesterolemia (TC < 250 mg/dl)
At least one of the following risk factor:
age (M > 55 years)
smoking
family history of premature CV disease
echocardiographic LVH
carotid wall thickening (IMT > 0.9 mm)
ankle/brachial BP < 0.9
Exclusion Criteria:
Secondary hypertension
Overweight or obese state (BMI ≥ 25 Kg/m2)
Suspected history of allergy to the ARBs, or ACEs
Malignancy
Renal, hepatic, endocrine, or gastrointestinal disease
Women who are pregnant and lactating
Women child-bearing potential
Heart failure
AMI and/or stroke in the previous 6 months
CHD
Diabetes mellitus
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Giuseppe Derosa, MD
Phone
+39 0382 502614
Email
giuseppe.derosa@unipv.it
First Name & Middle Initial & Last Name or Official Title & Degree
Roberto Fogari, MD
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giuseppe Derosa, MD
Organizational Affiliation
University of Pavia
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pavia
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giuseppe Derosa, MD
Phone
+39 0382 502614
Email
giuseppe.derosa@unipv.it
First Name & Middle Initial & Last Name & Degree
Roberto Fogari, MD
Phone
+39 0382 526217
Email
r.fogari@unipv.it
First Name & Middle Initial & Last Name & Degree
Giuseppe Derosa, MD
12. IPD Sharing Statement
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Imidapril and Candesartan on Fibrinolysis and Insulin-Sensitivity in Patients With Mild to Moderate Hypertension
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