Essential HypertensionPhase 3NCT00644475
Imidapril and Candesartan on Fibrinolysis and Insulin-Sensitivity in Patients With Mild to Moderate Hypertension
A Phase 3 study testing Imidapril and Candesartan in people with Essential Hypertension, run by University of Pavia at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Essential Hypertension
- What is being tested?
- Imidapril and Candesartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteItaly
- Study dates
- Mar 2008to Mar 2009
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- Women child-bearing potential
- Heart failure
- AMI and/or stroke in the previous 6 months
- CHD
- Diabetes mellitus
Trial locations and contacts
1 site in 1 country.
Roberto Fogari, MD contact
Italy1 site, 1 recruiting
- Recruiting
University of Pavia
Pavia, 27100
Giuseppe Derosa, MD, +39 0382 502614, giuseppe.derosa@unipv.it
Roberto Fogari, MD, +39 0382 526217, r.fogari@unipv.it
About this study
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
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
- Being tested
- Imidapril, Candesartan
- Keywords
- Hypertension, Insulin sensitivity, Fibrinolysis
- Medical subject headings
- Essential Hypertension, Hypertension, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImidaprilDrug
Also called Not yet registered in Italy
tablets; 5, 10, 15, 20 mg; od; 12 weeks
CandesartanDrug
Also called Registered in Italy
tablets; 8, 16, 24, and 32 mg; od; 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| 2 | Experimental | Imidapril Receives: Drug: Imidapril |
| 1 | Active comparator | Candesartan Receives: Drug: Candesartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
PAI-1 level and t-PA activity time course changes
Measured: 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
Measured: 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
Measured: 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 outcomes (1)
Blood pressure changes
Measured: At 0, 1, 2, 4, 8, and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2008 (estimated)
- Study startMar 2008
- Primary completionMar 2008
- Study completionMar 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Essential HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pavia
- Sponsor type
- University, hospital or other
- Investigators
- Giuseppe Derosa, MD, Principal investigator, University of Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00644475
- Sponsor's protocol ID
- UNIPV001DIM2008
- Status last verified
- Mar 2008
- First submitted
- 12 Mar 2008
- Last updated
- 26 Mar 2008
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00644475
- Acronym / sponsor ID
- UNIPV001DIM2008
- Conditions
- Essential Hypertension
- Keywords
- Hypertension, Insulin sensitivity, Fibrinolysis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of PaviaUniversity, hospital or other
- Study start
- Mar 2008
- Primary completion
- Mar 2008 (actual)
- Study completion
- Mar 2009 (estimated)
- First posted
- 26 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2 | Experimental | Drug: ImidaprilImidapril |
| 1 | Active comparator | Drug: CandesartanCandesartan |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImidaprilAlso: Not yet registered in Italytablets; 5, 10, 15, 20 mg; od; 12 weeks | Drug | 2 |
| CandesartanAlso: Registered in Italytablets; 8, 16, 24, and 32 mg; od; 12 weeks | Drug | 1 |
Primary outcome
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
1 secondary outcome
Blood pressure changes
Time frame: At 0, 1, 2, 4, 8, and 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roberto Fogari, MD contact
Giuseppe Derosa, MD principal investigator
University of Pavia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Imidapril and Candesartan in people with Essential Hypertension, run by University of Pavia at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Giuseppe Derosa, MD (+39 0382 502614, giuseppe.derosa@unipv.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2008.