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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2008 by University of Pavia.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Pavia
ClinicalTrials.gov Identifier:
NCT00644475
First received: March 12, 2008
Last updated: March 25, 2008
Last verified: March 2008
  Purpose

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 Intervention Phase
Essential Hypertension
Drug: Imidapril
Drug: Candesartan
Phase 3

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

Resource links provided by NLM:


Further study details as provided by University of Pavia:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Blood pressure changes [ Time Frame: At 0, 1, 2, 4, 8, and 12 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: March 2008
Estimated Study Completion Date: March 2009
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 2
Imidapril
Drug: Imidapril
tablets; 5, 10, 15, 20 mg; od; 12 weeks
Other Name: Not yet registered in Italy
Active Comparator: 1
Candesartan
Drug: Candesartan
tablets; 8, 16, 24, and 32 mg; od; 12 weeks
Other Name: Registered in Italy

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00644475

Contacts
Contact: Giuseppe Derosa, MD +39 0382 502614 giuseppe.derosa@unipv.it
Contact: Roberto Fogari, MD

Locations
Italy
University of Pavia Recruiting
Pavia, Italy, 27100
Contact: Giuseppe Derosa, MD    +39 0382 502614    giuseppe.derosa@unipv.it   
Contact: Roberto Fogari, MD    +39 0382 526217    r.fogari@unipv.it   
Principal Investigator: Giuseppe Derosa, MD         
Sponsors and Collaborators
University of Pavia
Investigators
Principal Investigator: Giuseppe Derosa, MD University of Pavia
  More Information

No publications provided

Responsible Party: Giuseppe Derosa/Aggregate Professor of Internal Medicine, University of Pavia
ClinicalTrials.gov Identifier: NCT00644475     History of Changes
Other Study ID Numbers: UNIPV001DIM2008
Study First Received: March 12, 2008
Last Updated: March 25, 2008
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by University of Pavia:
Hypertension
Insulin sensitivity
Fibrinolysis

Additional relevant MeSH terms:
Hypertension
Insulin Resistance
Vascular Diseases
Cardiovascular Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Imidapril
Candesartan
Candesartan cilexetil
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on July 20, 2014