Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03830944 |
| Other study ID # |
CM0119-VIA |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 25, 2019 |
| Est. completion date |
March 1, 2022 |
Study information
| Verified date |
July 2019 |
| Source |
Cardio Med Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
VIABILITY study aims to investigate the link between systemic inflammation, pancoronary
plaque vulnerability (referring to the plaque vulnerability within the entire coronary tree),
myocardial viability and ventricular remodeling in patients who had suffered a recent
ST-segment elevation acute myocardial infarction (STEMI). The level of systemic inflammation
in the acute phase of the myocardial infarction and at 1 month will be assessed on the basis
of serum levels of inflammatory biomarkers (hsCRP, matrix metalloproteinases, interleukin-6).
Pancoronary plaque vulnerability will be assessed: (1) in the acute phase of the infarction,
based on serum biomarkers known to be associated with increased plaque vulnerability, such as
adhesion molecules (V-CAM or I-CAM) determined from the blood samples collected in the first
day after STEMI; (2) at 1 month after infarction, based on computed tomographic angiography
analysis of vulnerability features present in all coronary plaques. Myocardial viability and
remodeling will be assessed based on: (1) 3D speckle tracking echocardiography associated
with dobutamine infusion; (2) MRI imaging associated with complex post-processing techniques
for mapping myocardial fibrosis and scar at the level of left atrium and left ventricle. At
the same time, CT imaging features associated with systemic and local inflammation, such as
global epicardial fat or local pericoronary epicardial fat will be quantified in order to
investigate the impact of inflammatory-mediated plaque vulnerability on the extent of
myocardial damage in acute myocardial infarction. All these parameters will be investigated
in patients with successful primary revascularization performed in a timely manner for
ST-segment elevation acute myocardial infarction, who will be divided into 2 groups: group 1
- patients who present persistence of an augmented inflammatory status defined as serum
levels of hsCRP>3.0 mg/dl at discharge from the hospital or at 7 days postinfarction
(whichever comes first), and group 2 - patients with no persistence of augmented inflammatory
status (hsCRP<3.0 mg/dl).
The primary endpoint of the study will be represented by the rate of post-infarction heart
failure development, defined as the rate of re-admission in the hospital for heart failure or
by a significant decrease in the ejection fraction (<45%).
The secondary endpoints of the study will be:
- rate of re-hospitalization
- rate of repeated revascularization
- rate of major adverse cardiovascular events (MACE rate, including cardiovascular death
or stroke)
Description:
Patients with acute myocardial infarction (AMI) who survive the acute event, very often
present a significant deterioration of their clinical status with progression towards heart
failure, which is directly linked to the extent of myocardial injury and the remodeling
process starting immediately after infarction. The major aim of the urgent revascularization
in STEMI is to save myocardial tissue from death and necrosis, in order to recover viable
myocardium. It is well-known that one of the major factors that trigger an AMI is the
systemic inflammation, which has a direct influence on coronary plaque vulnerability. At the
same time, 20% of patients surviving an AMI present a recurrent cardiovascular event in the
following 12 months, as a result of increased systemic inflammation triggered by the
infarction, which leads to vulnerabilization of other atheromatous plaques from all the
circulatory system in the post-infarction period. While the role of inflammation in acute
coronary events is well established, the impact of inflammatory-mediated vulnerability of
coronary plaques from the entire coronary tree on the extension of ventricular remodeling and
scaring has not been elucidated so far.
This is a clinical prospective, descriptive, single-center study which will be carried out in
the University of Medicine, Pharmacy, Science and Technology Tîrgu Mures, Romania, in
collaboration with two clinical sites: Center of Advanced Research in Multimodal Cardiac
Imaging Cardio Med Tîrgu Mures, Romania and County Clinical Emergency Hospital Tîrgu Mures,
Romania. The duration of the study is 2 years which includes the initial screening and the
follow-up period.
The study will enroll 100 subjects with STEMI who underwent successful revascularization of
the culprit lesion in the first 12 hours after the onset of symptoms. Imaging biomarkers and
laboratory analyses such as: high sensitive C Reactive Protein (hsCRP), matrix
metalloproteinases (MMP), interleukin-6 (IL6) and N-Terminal Pro-B-Type Natriuretic Peptide
(NT pro-BNP) will be determined in the first 24 hours after the index hospitalization. At 1
month postinfarction all patients will undergo Dobutamine stress test associated with speckle
tracking echocardiography for evaluation of myocardial function and viability, CMR for
assessment of myocardial scar, function and remodeling, and Multislice Angio CT for
assessment of pancoronary vulnerability, by complex characterization of vulnerability
features in all the coronary plaques present in the coronary tree. All these parameters will
be investigated in patients with successful primary percutaneous coronary revascularization,
who will be divided into 2 groups: group 1 -patients with persistent elevation of systemic
inflammatory biomarkers at discharge from the hospital or at day 7 (whichever comes first)
(inflammation+ group); and group 2 - patients with no persistent elevation of systemic
inflammatory biomarkers at discharge from the hospital or at day 7 (whichever comes first)
(inflammation- group). In all patients, the following biomarkers will be determined: serum
levels of inflammatory biomarkers, adhesion molecules and NT-proBNP at 24 hours and 7 days
post procedure, the amount of myocardial fibrosis and scar in the left ventricle at 1 month,
the degree of ventricular remodeling and myocardial perfusion at 1 month and the amount of
epicardial fat surrounding the heart and the plaques. The study will be conducted over a
period of 2 years, in which patients will be examined at baseline, and will be followed-up
for MACE incidence.
All patients will sign an informed written consent and will be checked for the exclusion
criteria prior to enrollment.
Study objectives:
Primary: To investigate the link between coronary inflammation-mediated plaque vulnerability,
myocardial viability and ventricular remodeling in the post-infarction period.
Secondary:
- To investigate the impact of systemic inflammation on structural remodeling of the left
ventricle in the post-infarction period
- To investigate the impact of local inflammatory response on pancoronary plaque
vulnerability following an acute myocardial infarction.
Study Timeline:
- Baseline - visit 1 (day 0)
- Obtain and document consent from participant on study consent form.
- Verify inclusion/exclusion criteria.
- Obtain demographic information, medical history, medication history, alcohol and tobacco
use history.
- Record results of physical examinations and 12-lead ECG.
- Collect blood specimens (complete blood count, biochemistry, inflammatory biomarkers,
acute adhesion molecules).
- Imaging procedures: transthoracic 2-D echocardiography/speckle tracking
- Visit 2 (day 7 / discharge from the hospital)
- -hsCRP
- Visit 3 (month 1)
- Coronary Computed Tomographic Angiography (vulnerability features, epicardial fat,
myocardial perfusion)
- Cardiac Magnetic Resonance (myocardial fibrosis/scar, remodeling, viability)
- Dobutamine stress echocardiography / speckle tracking (viability)
- Visit 4,5,6 (month 3,6,9)
- Record results of physical examinations, 12-lead ECG and medical history.
- Imaging procedures: transthoracic 2-D echocardiography
- Final study visit (month 12)
- Record results of physical examinations, medical history,12-lead ECG
- Imaging procedures: transthoracic 2-D echocardiography
- End-point evaluation.
Study procedures:
- Medical history, clinical examination, laboratory tests (complete blood count,
biochemistry, serum level of hs-CRP, MMP, IL6, NT-pro-BNP, adhesion molecules);
- 12-lead ECG
- 2D transthoracic echocardiography with measurement of: cardiac diameters, volumes, left
ventricular systolic and diastolic function, speckle tracking echo, dobutamine viability
test.
- Late Gadolinium-Enhancement Cardiac Magnetic Resonance (LGE-CMR) with the evaluation of
myocardial scar and fibrosis, ventricular function and remodeling index.
- Angio Computed Tomography with assessment of coronary plaque vulnerability (based on
vulnerability features: positive remodeling, spotty calcification, napkin-ring sign, low
density plaque) and myocardial perfusion Data collection: All the information will be
collected in a database that consists of patient's background, medical history,
medication, imaging features provided by cardiac ultrasound, Cardiac magnetic resonance,
Angio CT and imaging post-processing data.
