- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00424801
Effects of Intensive Long-Term Vasodilation in Hypertensive Patients With Microvascular Angina Pectoris
Intensive Non-Sympathetic Activating Vasodilatory Treatment in Hypertensive Patients With Microvascular Angina Pectoris
Study Overview
Status
Conditions
Detailed Description
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
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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-
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Aarhus, Denmark, 8000
- Aarhus Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- hypertension
- angina pectoris CCS class II-IV
- objective signs of ischemia on exercise-ECG or myocardial SPECT
- no significant stenosis on angiography (minimal lumen diameter >50% of relevant reference segment)
Exclusion Criteria:
- known allergy to any study medication
- abnormal lab tests of clinical significance
- valvular disease of haemodynamic significance
- known secondary hypertension
- atrial fibrillation or other significant arrythmias
- myocardial infarction < 30 days before inclusion
- resting angina < one week before inclusion
- known endocrine disease, nephropathy or hepatic disease
- present malignant disease
- pregnancy
- fertile women not using safe contraceptives > 6 months before inclusion. Use of contraceptives must continue 1 month after completion or retraction from the study
- body mass index > 30
- significant chronic obstructive lung disease (FEV1 < 1.5 l)
- participant in another study including test medicine
- present treatment with dipyridamole
- present treatment with phosphodiesterase-5-inhibitors that the patient does not want to discontinue during the study period
- heart transplanted patients
- patients with magnetizable metallic implants
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Vasodilatory
Patients in this arm will receive intensive vasodilatory treatment to lower blood pressure
|
Individual titration, max.
dose 20 mg OD for 8 months
Other Names:
Individual titration, max.
dose 160 mg OD for 8 months
Other Names:
Individual titration, max.
dose 20 mg BD for 8 months
Other Names:
Individual titration, max.
dose 4 mg OD for 8 months
Other Names:
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 Names:
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 Names:
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Minimal coronary resistance
Time Frame: 8 months
|
8 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Peripheral vascular resistance
Time Frame: 8 months
|
8 months
|
Work capacity
Time Frame: 8 months
|
8 months
|
Ischemia threshold
Time Frame: 8 months
|
8 months
|
Collaborators and Investigators
Sponsor
Investigators
- 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
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Myocardial Ischemia
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Pain
- Neurologic Manifestations
- Chest Pain
- Angina Pectoris
- Microvascular Angina
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Antihypertensive Agents
- Vasodilator Agents
- Natriuretic Agents
- Micronutrients
- Membrane Transport Modulators
- Serotonin Agents
- Serotonin Antagonists
- Diuretics
- Sodium Channel Blockers
- Vitamins
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Angiotensin II Type 1 Receptor Blockers
- Angiotensin Receptor Antagonists
- Vitamin B Complex
- Diuretics, Potassium Sparing
- Sodium Chloride Symporter Inhibitors
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Acid Sensing Ion Channel Blockers
- Epithelial Sodium Channel Blockers
- Valsartan
- Hydrochlorothiazide
- Nicorandil
- Doxazosin
- Moxonidine
- Amiloride
- Pindolol
- Lercanidipine
Other Study ID Numbers
- Vasointense
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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