Evaluation of The Effects of Nebivolol in Comparison to Atenolol on Wall Shear Stress and Rupture Prone Coronary Plaques

Atherosclerosis Clinical Trial

Official title:

The Evaluation of The Effects of Nebivolol in Comparison to Atenolol on Wall Shear Stress and Rupture Prone Coronary Artery Plaques in Patients With Moderate Coronary Artery Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01230892
• Other study ID #: IRB00027953
• Secondary ID: Emory #00000681
• Status: Completed
• Phase: Phase 4
• First received: September 10, 2010
• Last updated: February 12, 2015
• Start date: February 2010
• Est. completion date: September 2013

Study information

• Verified date: February 2015
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Nebivolol is a novel blood pressure lowering drug with an additional effect on the inner lining of blood vessels to release a compound called nitric oxide that can relax blood vessels. Atenolol is a blood pressure reducing agent without the ability to release nitric oxide and effect additional blood vessel relaxation.

The goal of this proposal is to compare Nebivolol and Atenolol with respect to the following parameters:

• Plaque within arteries supplying the heart in terms of its volume and composition as assessed by ultrasound within these arteries.

• Ability of small arteries in the heart to open up and deliver an enhanced blood supply in response to drug called Adenosine (routinely used in the cardiac catheterization laboratory) as assessed by pressure and flow detecting catheters within these arteries.

• Ability of the inner lining of arteries that supply the heart to release a relaxing compound called nitric oxide in response to injection of Acetylcholine (also used in the cardiac catheterization laboratory) as assessed by squirting dye into these arteries

• Local forces that affect blood flow in the arteries supplying the heart as assessed by superimposing the above data into complex maps created offline at Georgia Institute of Technology.

It is likely that Nebivolol causes the plaque within arteries supplying the heart to change from the 'vulnerable' type to the 'stable' type plaque. There are several features of "vulnerable plaques" that can be detected in arteries of the heart using intravascular ultrasound (a small ultrasound camera that goes in the arteries of the heart). The investigators hypothesis is that Nebivolol will prove superior to Atenolol in reducing 'vulnerable plaques', improve blood flow within the small arteries and the health of inner lining of these arteries at the 1 year time point. The investigators plan to enroll 20 patients into the study (26 patient including dropouts) who will be randomized in a 1:1 manner to Nebivolol Vs Atenolol for 1 year and repeat evaluation at that time point.

Description:

Primary hypothesis:

Nebivolol therapy will reduce the number of thin-cap fibroatheromas, VH-IVUS defined "vulnerable plaques" compared to Atenolol in patients undergoing serial angiography and IVUS.

Secondary Hypotheses:

• Nebivolol therapy will improve coronary microvascular function

• Nebivolol therapy will improve coronary endothelial function

• Nebivolol therapy will improve coronary wall shear stress

Specific Aims:

To evaluate, in patients with stable angina or acute coronary syndromes and moderate angiographic coronary artery disease, the effects of Nebivolol 5 mg a day compared to Atenolol 50 mg a day on:

• The number of thin cap fibroatheromas, percent necrotic core, and percent atheroma volume as defined by the novel Virtual Histology IVUS (VH™ IVUS).

• The coronary shear stress profile measured using 3 dimensional vessel reconstruction, flow velocity measurements, and computational fluid dynamics.

• Microvascular function as determined by coronary flow reserve and fractional flow reserve measured by invasive Doppler/pressure assessment.

• Endothelial function as determined by the response of quantitative coronary angiography and Doppler assessment to intracoronary acetylcholine challenge.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 79 Years

Eligibility

Inclusion Criteria:

• Patients with stable angina or acute coronary syndrome

• Moderate coronary lesion (defined as a lesion significant enough by the treating physician to warrant further evaluation using CFR or FFR or intravascular ultrasound assessment).

• Lesion located in the proximal 60mm of the RCA or LAD.

• On stable medical therapy for other cardiac risk factors.

Exclusion Criteria:

• Left Main lesion greater than 50% stenosis

• Patients with a history of coronary artery bypass surgery

• Severe valvular heart disease

• Patients presenting with a STEMI.

• Inability to provide informed consent prior to randomization

• Creatinine >1.5

• Lesions located beyond 60mm in an epicardial vessel

• Coronary anatomy requiring CABG

• B-blocker, calcium channel blocker or extended-release nitrate therapy within last 48 hours.

• Bradycardia (HR<50 bpm)

• Hypotension (SBP<100mmHg)

• Severe COPD by pulmonary function testing

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis
• Endothelial Function

Intervention

Drug:
• Nebivolol
10 mg PO qday
• Atenolol
100 mg PO qday

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	Georgia Institute of Technology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Reduction of Thin-cap Fibroatheromas (TCFA) as Defined by VH-IVUS	Presence of thin-cap fibroatheroma as defined by virtual histology-intravascular ultrasound (VH-IVUS)	1 year	No