Effects of Intensive Long-Term Vasodilation in Hypertensive Patients With Microvascular Angina Pectoris
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|ClinicalTrials.gov Identifier: NCT00424801|
Recruitment Status : Terminated (Due to recent findings relating MRI contrast to nephrogenic systemic fibrosis)
First Posted : January 22, 2007
Last Update Posted : May 6, 2009
|Condition or disease||Intervention/treatment||Phase|
|Microvascular Angina Hypertension||Drug: Lercanidipine Drug: Valsartan Drug: Nicorandil Drug: Doxazosin Drug: Moxonidin Drug: Pindolol Drug: Amiloride, hydrochlorothiazide||Not Applicable|
Patients with hypertension frequently develop angina pectoris. This can be caused by either epicardial stenotic disease or, equally frequent, by increased resistance in small resistance vessels - microvascular dysfunction. This increased resistance is caused by a process called remodelling, where the existing material in the vessel wall is rearranged around a smaller lumen, whereas the sensitivity of the smooth muscle cells to agonist stimuli is unchanged. Under resting conditions the resistance is determined by both the tone in the smooth muscle cells in the vessel walls and the structure of the vessels themselves (RREST). Under hyperemic conditions the muscles relax and the resistance is determined only by vessel structure (RMIN).
A literature survey of the various studies on this subject has shown that structural changes relates to tone rather than blood pressure. This suggests that resistance vessel structure will be normalized only by an antihypertensive treatment which normalizes RREST i.e. rely on vasodilatation as a cause of the antihypertensive effect more than reduction of cardiac output.
The main hypothesis is, that it is possible to reverse the structural changes in the resistance vessels by vasodilatory treatment for eight months, thereby achieving lower coronary and peripheral minimal resistance (as determined by MRI and plethysmography, respectively), higher work capacity on exercise-ECG and less tendency to angina in these patients.
We will include 80 patients with essential hypertension, angina pectoris CCS class II-III and signs of ischemia on exercise-ECG or myocardial SPECT, but without significant stenosis in angiography. The patients are randomised, in a parallel, open-label design, to either vasodilatory (lercanidipine, valsartan, doxazosin and nicorandil) or standard treatment (metoprolol, diltiazem and isosorbide mononitrate). The aim of treatment in both arms is BP below 120/80 and the protocol allows further add-on therapy to reach this goal. The patients will be followed for eight months with a titration period of two months. MRI, plethysmography, exercise-ECG and echocardiography will be performed before and after the study period. The primary endpoint is minimal coronary resistance as determined by MRI; secondary endpoints are peripheral vascular resistance as determined by plethysmography, work capacity and ischemia threshold on exercise-ECG or myocardial SPECT.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Intensive Non-Sympathetic Activating Vasodilatory Treatment in Hypertensive Patients With Microvascular Angina Pectoris|
|Study Start Date :||January 2007|
|Estimated Primary Completion Date :||December 2008|
|Estimated Study Completion Date :||December 2008|
Patients in this arm will receive intensive vasodilatory treatment to lower blood pressure
Individual titration, max. dose 20 mg OD for 8 months
Other Name: Zanidip
Individual titration, max. dose 160 mg OD for 8 months
Other Name: Diovan
Individual titration, max. dose 20 mg BD for 8 months
Other Name: Angicor
Individual titration, max. dose 4 mg OD for 8 months
Other Name: Doxazosin "Stada"
Possible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 0,2 mg OD for 8 months
Other Name: Moxonidin "Alpharma"
Possible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 10 mg OD for 8 months
Other Name: Visken
Drug: Amiloride, hydrochlorothiazide
Possible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 1 tbl. OD for 8 months
Other Name: Sparkal
- Minimal coronary resistance [ Time Frame: 8 months ]
- Peripheral vascular resistance [ Time Frame: 8 months ]
- Work capacity [ Time Frame: 8 months ]
- Ischemia threshold [ Time Frame: 8 months ]
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): NCT00424801
|Aarhus, Denmark, 8000|
|Principal Investigator:||Michael N Præstholm, MD||University of Aarhus|
|Study Director:||Kent L Christensen, MD, DrMSc||Aarhus Hospital, medical-cardiologic dept. A|
|Study Director:||Won Yong Kim, MD, DrMSc||Skejby Hospital, cardiologic dept. B|
|Study Director:||Hans Erik Bøtker, MD, DrMSc||Skejby Hospital, cardiologic dept. B|