Ignite Creation Date:
2024-05-06 @ 9:27 AM
Last Modification Date:
2024-10-26 @ 12:14 PM
Study NCT ID:
NCT02985112
Status:
UNKNOWN
Last Update Posted:
2016-12-12
First Post:
2016-12-05
Brief Title:
INTegrated Assessment of intERmediate Coronary Stenoses by Fractional Flow rEserve FFR and Near-infraREd Spectroscopy NIRS
Sponsor:
SM Misericordia Hospital
Organization:
SM Misericordia Hospital
Study Overview
Official Title:
INTegrated Assessment of intERmediate Coronary Stenoses by Fractional Flow rEserve FFR and Near-infraREd Spectroscopy NIRS
Status:
UNKNOWN
Status Verified Date:
2016-12
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
INTERFERE
Brief 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 080 are indeed associated with a higher rate of adverse event and requires coronary revascularization whereas lesions with FFR 080 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 080 and non-significant FFR 080 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
Detailed 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 080 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 080 can be safely deferred incidence of MACE 1 with medical treatment only Conversely stenoses with an FFR 080 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 080 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 32-F rapid exchange catheter InfraReDx BurlingtonMassachusetts 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 080 and non-significant FFR 080 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 080 vs lesions with FFR 080
Secondary endpoints 1 lipid content expressed as LCBImax mean SD in lesions with FFR 080 vs lesions with FFR 080 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 005 a sample of 150 lesions will provide the study 80 power to meet the primary end point
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 080 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 32-F rapid exchange catheter InfraReDx BurlingtonMassachusetts 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 080 and non-significant FFR 080 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 080 vs lesions with FFR 080
Secondary endpoints 1 lipid content expressed as LCBImax mean SD in lesions with FFR 080 vs lesions with FFR 080 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 005 a sample of 150 lesions will provide the study 80 power to meet the primary end point
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None