AtherosclerosisPhase 4NCT01230892
Evaluation of The Effects of Nebivolol in Comparison to Atenolol on Wall Shear Stress and Rupture Prone Coronary Plaques
A Phase 4 study testing Nebivolol and Atenolol in people with Atherosclerosis and Endothelial Function, run by Emory University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 21 to 79 years
- Conditions the study is for
- Atherosclerosis, Endothelial Function
- What is being tested?
- Nebivolol and Atenolol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2010to Sep 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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:
Read more
- 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.
Read the 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.
- Conditions
- Atherosclerosis, Endothelial Function
- Being tested
- Nebivolol, Atenolol
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NebivololDrug
Also called Bystolic
10 mg PO qday
AtenololDrug
Also called Senormin, Tenormin
100 mg PO qday
| Study group | Role | What they receive |
|---|---|---|
| Nebivolol | Active comparator | Not described Receives: Drug: Nebivolol |
| Atenolol | Active comparator | Not described Receives: Drug: Atenolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2010 (estimated)
- Study startFeb 2010
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Georgia Institute of Technology
- Responsible party
- Principal investigator, Habib Samady, Emory University
- Investigators
- Habib Samady, MD, FACC, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01230892
- Sponsor's protocol ID
- IRB00027953
- Other IDs
- Emory #00000681
- Status last verified
- Feb 2015
- First submitted
- 10 Sep 2010
- Last updated
- 27 Feb 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Hung OY, Molony D, Corban MT, Rasoul-Arzrumly E, Maynard C, Eshtehardi P, Dhawan S, Timmins LH, Piccinelli M, Ahn SG, Gogas BD, McDaniel MC, Quyyumi AA, Giddens DP, Samady H. Comprehensive Assessment of Coronary Plaque Progression With Advanced Intravascular Imaging, Physiological Measures, and Wall Shear Stress: A Pilot Double-Blinded Randomized Controlled Clinical Trial of Nebivolol Versus Atenolol in Nonobstructive Coronary Artery Disease. J Am Heart Assoc. 2016 Jan 25;5(1):e002764. doi: 10.1161/JAHA.115.002764.
PubMed 26811165
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01230892
- Acronym / sponsor ID
- IRB00027953
- Conditions
- Atherosclerosis, Endothelial Function
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Georgia Institute of Technology
- Study start
- Feb 2010
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 29 Oct 2010 (estimated)
- Results
- Posted 27 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nebivolol | Active comparator | Drug: Nebivolol |
| Atenolol | Active comparator | Drug: Atenolol |
Who may qualify
- Ages
- 21 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NebivololAlso: Bystolic10 mg PO qday | Drug | Nebivolol |
| AtenololAlso: Senormin, Tenormin100 mg PO qday | Drug | Atenolol |
Primary outcome
Number of Participants With Reduction of Thin-cap Fibroatheromas (TCFA) as Defined by VH-IVUS
Time frame: 1 year
Presence of thin-cap fibroatheroma as defined by virtual histology-intravascular ultrasound (VH-IVUS)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26811165Hung OY, Molony D, Corban MT, Rasoul-Arzrumly E, Maynard C, Eshtehardi P, Dhawan S, Timmins LH, Piccinelli M, Ahn SG, Gogas BD, McDaniel MC, Quyyumi AA, Giddens DP, Samady H. Comprehensive Assessment of Coronary Plaque Progression With Advanced Intravascular Imaging, Physiological Measures, and Wall Shear Stress: A Pilot Double-Blinded Randomized Controlled Clinical Trial of Nebivolol Versus Atenolol in Nonobstructive Coronary Artery Disease. J Am Heart Assoc. 2016 Jan 25;5(1):e002764. doi: 10.1161/JAHA.115.002764.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Habib Samady, MD, FACC principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nebivolol and Atenolol in people with Atherosclerosis and Endothelial Function, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Reduction of Thin-cap Fibroatheromas (TCFA) as Defined by VH-IVUS (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01230892, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2015.