Intensive Vasodilator Therapy in Patients With Essential Hypertension (Vasomore)

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

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.

Study Overview

• Status: Completed
• Conditions: Essential Hypertension; High Blood Pressure
• Intervention / Treatment: Drug: Amlodipine; Drug: Ramipril; Drug: Lercanidipine; Drug: Losartan

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 Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital - dept. cardiology (A)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary Flow Reserve	Determined by echocardiography	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Puls Wave Velocity		6 months
Left ventricular mass	Determined with echocardiography	6 months
Blood Pressure	Ambulatory Blood Pressure	6 months
Peripheral Vascular Resistance	By Innocor	6 months
Minimal forearm vascular resistance	By pletysmography	6 months

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: 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

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (ACTUAL): April 1, 2012
• Study Completion (ACTUAL): April 1, 2012

Study Registration Dates

• First Submitted: August 11, 2010
• First Submitted That Met QC Criteria: August 11, 2010
• First Posted (ESTIMATE): August 12, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 19, 2012
• Last Update Submitted That Met QC Criteria: April 18, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Inward eutrophic remodelling
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Protease Inhibitors; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Amlodipine; Losartan; Ramipril; Lercanidipine
• Other Study ID Numbers: 26169