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
  Purpose

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


Condition Intervention
Microvascular Angina
Hypertension
Drug: Lercanidipine
Drug: Valsartan
Drug: Nicorandil
Drug: Doxazosin
Drug: Moxonidin
Drug: Pindolol
Drug: Amiloride, hydrochlorothiazide

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intensive Non-Sympathetic Activating Vasodilatory Treatment in Hypertensive Patients With Microvascular Angina Pectoris

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • Minimal coronary resistance [ Time Frame: 8 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 10
Study Start Date: January 2007
Estimated Study Completion Date: December 2008
Estimated Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vasodilatory
Patients in this arm will receive intensive vasodilatory treatment to lower blood pressure
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00424801

Locations
Denmark
Aarhus Hospital
Aarhus, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Danish Cardiovascular Research Academy
Danish Heart Foundation
Novartis
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
  More Information

No publications provided

Responsible Party: Kent Lodberg Christensen, DMSc, Aarhus Hospital
ClinicalTrials.gov Identifier: NCT00424801     History of Changes
Other Study ID Numbers: Vasointense
Study First Received: January 19, 2007
Last Updated: May 5, 2009
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency

Additional relevant MeSH terms:
Angina Pectoris
Hypertension
Microvascular Angina
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Amiloride
Hydrochlorothiazide
Lercanidipine
Moxonidine
Valsartan
Pindolol
Nicorandil
Doxazosin
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Acid Sensing Ion Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Epithelial Sodium Channel Blockers
Diuretics, Potassium Sparing
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 19, 2014