Imidapril and Candesartan on Fibrinolysis and Insulin-Sensitivity in Patients With Mild to Moderate Hypertension

NCT ID: NCT00644475

Last Updated: 2008-03-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2009-03-31

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.

Conditions

Essential Hypertension

Keywords

Hypertension; Insulin sensitivity; Fibrinolysis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

2

Imidapril

Group Type: EXPERIMENTAL

Imidapril

Intervention Type: DRUG

tablets; 5, 10, 15, 20 mg; od; 12 weeks

1

Candesartan

Group Type: ACTIVE_COMPARATOR

Candesartan

Intervention Type: DRUG

tablets; 8, 16, 24, and 32 mg; od; 12 weeks

Interventions

Imidapril

tablets; 5, 10, 15, 20 mg; od; 12 weeks

Intervention Type: DRUG

Candesartan

tablets; 8, 16, 24, and 32 mg; od; 12 weeks

Intervention Type: DRUG

Other Intervention Names

Not yet registered in Italy; Registered in Italy

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pavia

OTHER

Sponsor Role: lead

Responsible Party

University of Pavia

Principal Investigators

Giuseppe Derosa, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pavia

Locations

University of Pavia

Pavia, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Giuseppe Derosa, MD

Role: CONTACT

Phone: +39 0382 502614

Email: giuseppe.derosa@unipv.it

Roberto Fogari, MD

Role: CONTACT

Facility Contacts

Giuseppe Derosa, MD

Role: primary

Roberto Fogari, MD

Role: backup

Other Identifiers

UNIPV001DIM2008

Identifier Type: -

Identifier Source: org_study_id