Imidapril and Candesartan on Fibrinolysis and Insulin-Sensitivity in Patients With Mild to Moderate Hypertension
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|ClinicalTrials.gov Identifier: NCT00644475|
Recruitment Status : Unknown
Verified March 2008 by University of Pavia.
Recruitment status was: Recruiting
First Posted : March 26, 2008
Last Update Posted : March 26, 2008
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.
|Condition or disease||Intervention/treatment||Phase|
|Essential Hypertension||Drug: Imidapril Drug: Candesartan||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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 Start Date :||March 2008|
|Actual Primary Completion Date :||March 2008|
|Estimated Study Completion Date :||March 2009|
tablets; 5, 10, 15, 20 mg; od; 12 weeks
Other Name: Not yet registered in Italy
Active Comparator: 1
tablets; 8, 16, 24, and 32 mg; od; 12 weeks
Other Name: Registered in Italy
- 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 ]
- 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 ]
- 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 ]
- Blood pressure changes [ Time Frame: At 0, 1, 2, 4, 8, and 12 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00644475
|Contact: Giuseppe Derosa, MD||+39 0382 email@example.com|
|Contact: Roberto Fogari, MD|
|University of Pavia||Recruiting|
|Pavia, Italy, 27100|
|Contact: Giuseppe Derosa, MD +39 0382 502614 firstname.lastname@example.org|
|Contact: Roberto Fogari, MD +39 0382 526217 email@example.com|
|Principal Investigator: Giuseppe Derosa, MD|
|Principal Investigator:||Giuseppe Derosa, MD||University of Pavia|