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

Essential Hypertension Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00644475
• Other study ID #: UNIPV001DIM2008
• Status: Recruiting
• Phase: Phase 3
• First received: March 12, 2008
• Last updated: March 25, 2008
• Start date: March 2008
• Est. completion date: March 2009

Study information

• Verified date: March 2008
• Source: University of Pavia
• Contact: Giuseppe Derosa, MD
• Phone: +39 0382 502614
• Email: giuseppe.derosa[@]unipv.it
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: March 2009
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension
• Insulin Resistance

Intervention

Drug:
• Imidapril
tablets; 5, 10, 15, 20 mg; od; 12 weeks
• Candesartan
tablets; 8, 16, 24, and 32 mg; od; 12 weeks

Locations

Country	Name	City	State
Italy	University of Pavia	Pavia

Sponsors (1)

Lead Sponsor	Collaborator
University of Pavia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PAI-1 level and t-PA activity time course changes		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	Yes
Primary	t-PA activity at the desmopressin test		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	Yes
Primary	Insulin sensitivity state through euglycemic hyperinsulinemic clamp method		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	Yes
Secondary	Blood pressure changes		At 0, 1, 2, 4, 8, and 12 weeks	Yes