Effects of Intensive Long-Term Vasodilation in Hypertensive Patients With Microvascular Angina Pectoris

May 5, 2009 updated by: University of Aarhus

Intensive Non-Sympathetic Activating Vasodilatory Treatment in Hypertensive Patients With Microvascular Angina Pectoris

The purpose of this study is to determine if long-term vasodilatory treatment is more effective than the standard treatment in hypertensive patients with microvascular angina pectoris

Study Overview

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

Interventional

Enrollment (Actual)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Aarhus, Denmark, 8000
        • Aarhus Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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:
  • Zanidip
Individual titration, max. dose 160 mg OD for 8 months
Other Names:
  • Diovan
Individual titration, max. dose 20 mg BD for 8 months
Other Names:
  • Angicor
Individual titration, max. dose 4 mg OD for 8 months
Other Names:
  • 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 Names:
  • 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 Names:
  • Visken
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:
  • Sparkal

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

This is where you will find people and organizations involved with this study.

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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2007

Primary Completion (Anticipated)

December 1, 2008

Study Completion (Anticipated)

December 1, 2008

Study Registration Dates

First Submitted

January 19, 2007

First Submitted That Met QC Criteria

January 19, 2007

First Posted (Estimate)

January 22, 2007

Study Record Updates

Last Update Posted (Estimate)

May 6, 2009

Last Update Submitted That Met QC Criteria

May 5, 2009

Last Verified

May 1, 2009

More Information

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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