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

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00424801
• Other study ID #: Vasointense
• Status: Terminated
• Phase: N/A
• First received: January 19, 2007
• Last updated: May 5, 2009
• Start date: January 2007
• Est. completion date: December 2008

Study information

• Verified date: May 2009
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina Pectoris
• Hypertension
• Microvascular Angina

Intervention

Drug:
• Lercanidipine
Individual titration, max. dose 20 mg OD for 8 months
• Valsartan
Individual titration, max. dose 160 mg OD for 8 months
• Nicorandil
Individual titration, max. dose 20 mg BD for 8 months
• Doxazosin
Individual titration, max. dose 4 mg OD for 8 months
• 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
• 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
• 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

Locations

Country	Name	City	State
Denmark	Aarhus Hospital	Aarhus

Sponsors (4)

Lead Sponsor	Collaborator
University of Aarhus	Danish Cardiovascular Research Academy, Danish Heart Foundation, Novartis

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Minimal coronary resistance		8 months	No
Secondary	Peripheral vascular resistance		8 months	No
Secondary	Work capacity		8 months	No
Secondary	Ischemia threshold		8 months	No