Vasomore: Intensive Vasodilator Therapy in Patients With Essential Hypertension

Sponsor

Aarhus University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01180413

Collaborator

University of Aarhus (Other)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether add-on of intensive vasodilator therapy can improve the coronary perfusion and reduce the total peripheral resistance in patients with ongoing treatment for essential hypertension.

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension High Blood Pressure	Drug: Amlodipine Drug: Ramipril Drug: Lercanidipine Drug: Losartan	Phase 4

Detailed Description

Morphological changes are observed in the microvasculature of patients with essential hypertension. The lumen diameter is reduced in resistance arteries, but with no change in vessel cross-sectional area or wall mass. These structural changes are termed inward eutrophic remodelling and results in an increased wall:lumen ratio, caused by rearrangement of cell matrix and not by hypertrophy of smooth muscle cells in the vascular wall as observed in secondary forms of hypertension. The morphological changes also occur in the coronary arteries and cause a reduction in the ability to increase coronary perfusion as response to increased cardiac work. This is observed as a reduced coronary flow reserve in patients with sustained hypertension.

Two recently published clinical studies associates an increase in media:lumen ratio with an increased risk of cardiovascular events, and it therefore seems beneficial to normalize the vascular structure in patients with essential hypertension. It has previously been demonstrated that reversion of vascular remodelling and thereby normalization of the vascular structure, requires vasodilatation and not just blood pressure reduction, suggesting that patients with essential hypertension can benefit from antihypertensive treatment aimed to induce vasodilatation.

The purpose of this study is to determine whether add-on of intensive vasodilator therapy can improve the coronary perfusion (coronary flow reserve) and reduce the total peripheral resistance in patients with ongoing treatment for essential hypertension. We also aim to investigate whether changes in coronary flow reserve correlates better to changes in total peripheral resistance than changes in blood pressure. Particularly we aim to study if patients with high total peripheral resistance, despite blood pressure control, can benefit from intensive vasodilating therapy.

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effects of Intensive Vasodilating add-on Therapy on Peripheral Vascular Resistance and Coronary Flow Reserve in Patients With Essential Hypertension

Study Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Apr 1, 2012

Actual Study Completion Date :

Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vasodilatory Patients in this arm will receive intensive vasodilatory treatment	Drug: Amlodipine 5 mg per day for 6 months as add-on to original ongoing antihypertensive treatment Other Names: Amlodipin Drug: Ramipril 5 mg per day for the first to weeks as add-on to original ongoing antihypertensive treatment. Then upward adjustment to 10 mg per day for 6 months if no intolerable side effects are experienced. Drug: Lercanidipine Up to 20 mg per day for 6 months as add-on to original ongoing antihypertensive treatment Drug: Losartan Up to 100 mg per day for 6 months as add-on to original ongoing antihypertensive treatment

Arm

Intervention/Treatment

Experimental: Vasodilatory

Patients in this arm will receive intensive vasodilatory treatment

Drug: Amlodipine

5 mg per day for 6 months as add-on to original ongoing antihypertensive treatment

Other Names:

Amlodipin

Drug: Ramipril

5 mg per day for the first to weeks as add-on to original ongoing antihypertensive treatment. Then upward adjustment to 10 mg per day for 6 months if no intolerable side effects are experienced.

Drug: Lercanidipine

Up to 20 mg per day for 6 months as add-on to original ongoing antihypertensive treatment

Drug: Losartan

Up to 100 mg per day for 6 months as add-on to original ongoing antihypertensive treatment

Outcome Measures

Primary Outcome Measures

Coronary Flow Reserve [6 months]
Determined by echocardiography

Secondary Outcome Measures

Puls Wave Velocity [6 months]
Left ventricular mass [6 months]
Determined with echocardiography
Blood Pressure [6 months]
Ambulatory Blood Pressure
Peripheral Vascular Resistance [6 months]
By Innocor
Minimal forearm vascular resistance [6 months]
By pletysmography

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ongoing antihypertensive treatment for >3 months
Blood pressure >120/75 during antihypertensive treatment
Ejection fraction > 45%

Exclusion Criteria:

Blood pressure >160/100
Pregnancy
fertile women not using safe contraceptives
known secondary hypertension
valvular disease of haemodynamic significance
known endocrine disease, nephropathy or hepatic disease
present malignant disease
known psychiatric disease
abnormal lab tests of clinical significance
known allergy to any study medication
body mass index > 35
Ongoing antihypertensive treatment with a combination of ACE-inhibitor and Calcium antagonist.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aarhus University Hospital - dept. cardiology (A)	Aarhus		Denmark	8000

Sponsors and Collaborators

Aarhus University Hospital
University of Aarhus

Investigators

Principal Investigator: Morten Engholm Pedersen, MD, Aarhus University and Aarhus University Hospital
Study Director: Ole Norling Mathiasen, MD, PhD, Aarhus University and Aarhus University Hospital
Study Director: Niels Henrik Buus, DMSc, Aarhus University and Aarhus University Hospital
Principal Investigator: Ashkan Eftekhari, MD, PhD, Aarhus University and Aarhus University Hospital