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

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01230892
• Collaborator: Georgia Institute of Technology (Other)
• Enrollment: 29
• Location: 1
• Arms: 2
• Duration (Months): 43
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis; Endothelial Function	Drug: Nebivolol; Drug: Atenolol	Phase 4

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nebivolol	Drug: Nebivolol; 10 mg PO qday; Other Names: Bystolic
Active Comparator: Atenolol	Drug: Atenolol; 100 mg PO qday; Other Names: Senormin Tenormin

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Reduction of Thin-cap Fibroatheromas (TCFA) as Defined by VH-IVUS [1 year]

   Presence of thin-cap fibroatheroma as defined by virtual histology-intravascular ultrasound (VH-IVUS)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University Hospital	Atlanta	Georgia	United States	30322

Sponsors and Collaborators

• Emory University
• Georgia Institute of Technology

Investigators

• Principal Investigator: Habib Samady, MD, FACC, Emory University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Habib Samady, Professor, Emory University
• ClinicalTrials.gov Identifier: NCT01230892
• Other Study ID Numbers: IRB00027953; Emory #00000681
• First Posted: Oct 29, 2010
• Last Update Posted: Feb 27, 2015
• Last Verified: Feb 1, 2015

• Additional relevant MeSH terms: Atherosclerosis; Rupture; Atenolol; Nebivolol

Study Results

Participant Flow

Arm/Group Title	Nebivolol	Atenolol
Arm/Group Description	Nebivolol: 10 mg PO qday	Atenolol: 100 mg PO qday
Period Title: Overall Study
STARTED	15	14
COMPLETED	12	13
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Nebivolol	Atenolol	Total
Arm/Group Description	Nebivolol: 10 mg PO qday	Atenolol: 100 mg PO qday	Total of all reporting groups
Overall Participants	12	12	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (10)	50 (11)	52 (10)
Sex: Female, Male (Count of Participants)
Female	8 66.7%	7 58.3%	15 62.5%
Male	4 33.3%	5 41.7%	9 37.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 33.3%	2 16.7%	6 25%
White	8 66.7%	10 83.3%	18 75%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Reduction of Thin-cap Fibroatheromas (TCFA) as Defined by VH-IVUS
Description	Presence of thin-cap fibroatheroma as defined by virtual histology-intravascular ultrasound (VH-IVUS)
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

4 subjects either withdrew or were lost to follow-up and not included in analysis population. Additionally, one subject in the Atenolol arm was removed from analysis population due to IVUS occurring in the incorrect artery and one subject in the Nebivolol arm was removed due to the IVUS catheter malfunctioning.

Arm/Group Title	Nebivolol	Atenolol
Arm/Group Description	Nebivolol: 10 mg PO qday	Atenolol: 100 mg PO qday
Measure Participants	11	12
Number [participants]	4 33.3%	6 50%

Adverse Events

Arm/Group Title	Nebivolol		Atenolol
Arm/Group Description	Nebivolol: 10 mg PO qday		Atenolol: 100 mg PO qday
All Cause Mortality
	Nebivolol		Atenolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Nebivolol		Atenolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Nebivolol		Atenolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.