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

This study has been terminated.
(Due to recent findings relating MRI contrast to nephrogenic systemic fibrosis)
Sponsor:
Collaborators:
Danish Cardiovascular Research Academy
Danish Heart Foundation
Novartis
Information provided by:
University of Aarhus
ClinicalTrials.gov Identifier:
NCT00424801
First received: January 19, 2007
Last updated: May 5, 2009
Last verified: May 2009

January 19, 2007
May 5, 2009
January 2007
December 2008   (final data collection date for primary outcome measure)
Minimal coronary resistance [ Time Frame: 8 months ] [ Designated as safety issue: No ]
Minimal coronary resistance
Complete list of historical versions of study NCT00424801 on ClinicalTrials.gov Archive Site
  • Peripheral vascular resistance [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • Work capacity [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • Ischemia threshold [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • Peripheral vascular resistance
  • Work capacity
  • Ischemia threshold
Not Provided
Not Provided
 
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

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

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.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Microvascular Angina
  • Hypertension
  • Drug: Lercanidipine
    Individual titration, max. dose 20 mg OD for 8 months
    Other Name: Zanidip
  • Drug: Valsartan
    Individual titration, max. dose 160 mg OD for 8 months
    Other Name: Diovan
  • Drug: Nicorandil
    Individual titration, max. dose 20 mg BD for 8 months
    Other Name: Angicor
  • Drug: Doxazosin
    Individual titration, max. dose 4 mg OD for 8 months
    Other Name: Doxazosin "Stada"
  • Drug: Moxonidin
    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"
  • Drug: Pindolol
    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
Experimental: Vasodilatory
Patients in this arm will receive intensive vasodilatory treatment to lower blood pressure
Interventions:
  • Drug: Lercanidipine
  • Drug: Valsartan
  • Drug: Nicorandil
  • Drug: Doxazosin
  • Drug: Moxonidin
  • Drug: Pindolol
  • Drug: Amiloride, hydrochlorothiazide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
10
December 2008
December 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT00424801
Vasointense
Yes
Kent Lodberg Christensen, DMSc, Aarhus Hospital
University of Aarhus
  • Danish Cardiovascular Research Academy
  • Danish Heart Foundation
  • Novartis
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
University of Aarhus
May 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP