Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02985112 |
| Other study ID # |
USL9-2015-007-NIRS |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
December 5, 2016 |
| Last updated |
December 9, 2016 |
| Start date |
March 2015 |
| Est. completion date |
December 2018 |
Study information
| Verified date |
December 2016 |
| Source |
S.M. Misericordia Hospital |
| Contact |
Andrea Picchi |
| Phone |
+390564483465 |
| Email |
andre.picchi[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
Italy: Ethics Committee |
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Revascularization of borderline coronary stenoses (40-70%) is usually driven by fractional
flow reserve (FFR) which expresses the physiological significance of a lesion and tells the
operator whether PCI may reduce the rate of adverse events as compared to medical therapy.
Coronary stenoses with FFR value < 0.80 are indeed associated with a higher rate of adverse
event and requires coronary revascularization whereas lesions with FFR > 0.80 show an
excellent prognosis which cannot be improved by coronary stenting. Such a predictive value
of FFR is theoretically based only on the degree of myocardial ischemia downstream from a
given coronary stenosis: however, also plaque composition may play a crucial role in
triggering future events especially in patients affected by acute coronary syndrome.
Differences in plaque composition between FFR-positive and FFR negative lesions have never
been assessed. Intracoronary Near-InfraRed Spectroscopy (NIRS) identifies lipid rich plaques
that can potentially cause acute events. The aim of this study is to compare the lipid
content expressed by LCBI (Lipid Core Burden Index) between functionally significant (FFR <
0.80) and non-significant (FFR > 0.80) stenoses in patients undergoing coronary angiography
because of stable CAD and non-ST elevation acute coronary syndromes. This is an
observational, prospective, multicentric study where we plan to collect 150 coronary
lesions.
Description:
Background Objective of percutaneous coronary intervention (PCI) is the treatment of
angiographically significant coronary stenoses in patients affected by stable or unstable
coronary syndromes 1. When we face an intermediate stenosis (percentage diameter stenosis
between 40% and 70%), revascularization is guided by the presence of inducible myocardial
ischemia, detected by non - invasive stress tests or by assessment of fractional flow
reserve (FFR). FFR is an index of the physiological significance of a coronary stenosis and
is defined as the ratio of maximal blood flow in a stenotic artery to normal maximal flow.
An FFR value of 0.80 or less identifies ischemia-causing coronary stenoses with an accuracy
of more than 90%. FFR is a very accurate tool to identify functionally significant stenoses
and to predict cardiovascular events in patients with stable coronary artery disease (CAD)
and solid evidences demonstrate that PCI of lesions with FFR > 0.80 can be safely deferred
(incidence of MACE < 1% with medical treatment only). Conversely, stenoses with an FFR <0.80
have a poor prognosis and require treatment by PCI 2-4. The afore-mentioned indications come
from studies that mainly involved patients affected by stable CAD, but the role of FFR in
the setting of acute coronary sindrome (ACS) is less clear. Hakeem et al. have recently
shown that deferring percutaneous coronary intervention on the basis of non-ischemic FFR in
patients with an initial presentation of ACS is associated with significantly worse outcomes
than stable patients5.
FFR indeed has the ability to identify vessels with reduced coronary flow, but cannot detect
atherosclerotic plaques with unstable features, which may present without flow limitation
(FFR > 0.80) but can cause acute coronary events 6, 7. Since the prevalence of features of
plaque instability (plaque volume > 70%, minimum luminal area <4 mm2, presence of a "thin
cap fibroatheroma") increase with the increase of the severity of the stenosis, the decision
of performing PCI for stenoses of clear angiographic severity seems rational and supported
by solid evidence 8. Conversely, delaying PCI of intermediate stenoses on the basis of a
negative FFR can be problematic, particularly in patients with ACS, where the only
functional evaluation with FFR may not be sufficient in the presence of unstable plaques.
Differences in plaque composition between physiologically significant vs non-significant
lesions have never been assessed in either stable and ACS patients.
Intracoronary Near-InfraRed Spectroscopy (NIRS) identifies lipid-rich plaques (LRP) with
high sensibility and specificity. The technique, validated on autopsy specimens, is an
effective tool to detect LRP in vivo, identifying those coronary atheromas that can
potentially cause acute events 9. The NIRS system consists of a 3.2-F rapid exchange
catheter (InfraReDx, Burlington,Massachusetts), a pullback and rotation device, and a
console. The measurement of the probability of LRP for each scanned arterial segment is
displayed as a map, with the x-axis indicating the pullback position in millimeters and the
y-axis the circumferential position of the measurement in degrees. The algorithm displays
the probability of lipid content at the interrogation site by using a false color scale from
red (low probability) to yellow (high probability). The entire display is termed a
"chemogram". Pixels containing insufficient informations are displayed as black. The ratio
between the number of yellow pixels to the whole number of pixels except the black ones,
multiplied by one - thousand, is the "Lipid Core Burden Index (LCBI)" of the analyzed artery
segment. A value of LCBImax > 400 identifies a high lipid content in a given segment. In an
autopsy study conducted on human aortic specimens, the technique reached 90% sensibility and
93 % specificity in the detection of lipid rich plaques9, opening new horizons in terms of
risk stratification and therapy10-15. To provide a quantitative target suitable for
algorithm construction and validation, a lipid core plaque of interest was defined as a
fibroatheroma with a lipid core > 60° in circumferential extent, >200 µm thick, with a
fibrous cap having a mean thickness < 450 µm16.
Aim of the study
- To compare lipid content expressed by LCBImax value between functionally significant
(FFR < 0.80) and non-significant (FFR > 0.80) stenoses in patients undergoing coronary
angiography because of stable CAD and non-ST elevation acute coronary syndromes.
- To evaluate the correlation between functional significance (expressed by FFR value)
and lipid content (expressed by LCBImax value) of coronary lesions in patients
undergoing coronary angiography because of stable CAD and non-ST elevation acute
coronary syndromes.
Design of the study This is an observational, prospective, multicentric study: at present
time, two centers (Misericordia Hospital, Grosseto and San Giovanni Hospital, Rome) are
going to take part in the study.
Subjects undergoing coronary angiography for stable CAD and non-ST-segment elevation acute
myocardial infarction (NSTEMI) and unstable angina will be enrolled. Patients included must
have evidence of at least one angiographically borderline stenosis (≥ 40, <70% by
Quantitative Coronary Angiography, QCA) with normal antegrade flow (TIMI 3). The index
lesion will be evaluated by FFR; afterwards, plaque composition and lesion characteristics
will be evaluated by IVUS - NIRS. PCI will be performed according to current guidelines on
myocardial revascularization1.
Patients with hemodynamic instability, ST-segment-elevation myocardial infarction, known
allergy to antiplatelet or anticoagulant drugs, history of previous CABG, significant left
main disease, life expectancy < 1 year, severe renal failure, malignancy, scheduled valve
surgery, inability to provide informed consent, known bronchial asthma, age < 18 will be
excluded.
Endpoints
- Primary endpoint: percentage of coronary plaques with LCBImax > 400 in lesions with FFR
> 0.80 vs lesions with FFR < 0.80. .
- Secondary endpoints: 1) lipid content expressed as LCBImax (mean ± SD) in lesions with
FFR > 0.80 vs lesions with FFR < 0.80. 2) Correlation between lipid content (as LCBI
max), and functional significance (as FFR) of the index lesion.
Sample size The sample size will be calculated to demonstrate a decrease in the primary end
point (percentage of coronary plaques with LCBImax > 400) from 36% in FFR positive lesions
to 18% in FFR negative lesions, as inferred by previous findings showing a 36% vs 18%
prevalence of thin cap fibroatheroma in lesions with a >70% vs <70% diameter stenosis17.
Using chi-square test for 2 x 2 tables and a 1-sided alpha value of 0.05, a sample of 150
lesions will provide the study 80% power to meet the primary end point.
