Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05810610 |
| Other study ID # |
IMAG-01-2022 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 2023 |
| Est. completion date |
December 2025 |
Study information
| Verified date |
March 2023 |
| Source |
Institut Mutualiste Montsouris |
| Contact |
Jean-François PAUL, MD |
| Phone |
0156616171 |
| Email |
Jean-Francois.Paul[@]imm.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The goal of this Category 3 research involving the human person is to predict the measurement
of the post-stenosis flow (FFR) using CTTA coupled with an intelligent predictive analysis
system and comparing it with invasive coronary angiography FFR as measurement of reference.
The population studied are adult patients,- with no diagnosed coronary status or history of
stenting or bypass surgery- with indication for FFR measurement.
The main question it aims to answer is:
• Can, in a single acquisition, CTTA coupled with AI produce good predictive performance of
stenosis and FFR ? If it can it will allow us to avoid the need for invasive FFR.
For patients who will be included in the retrospective part: only their data from their
medical records will be used.
Patients who will be included in the prospective part will additionally complete the EQ5D5L
questionnaire before coronary angiography and at the end of the patient's participation (4
months after the CCTA).
There is a no comparison group, the predictive FFR from CTTA of a patient will be compared
with angiography FFR from the same patient, same vessel.
Description:
Coronary disease is the leading cause of death in the world with 18 million deaths according
to the WHO The exploration of chest pain suggesting coronary artery disease now gives
preference to coronary CT angiography (CCTA) for its high sensitivity (95%) in the
non-invasive detection of patients with coronary artery disease.
This is a class I recommendation with a high level of evidence according to the AHA/ACC
recommendations of November 2021. The interpretation of the images aims to define the degree
of stenosis of the vessels, a stenosis >= 50% being likely to limit coronary flow. However,
the degree of stenosis, especially between 40%-90%, is not directly correlated with its
functional impact. This must therefore be assessed by an invasive intra-arterial examination
during coronary angiography. The measurement of the post-stenosis flow (FFR) may indicate a
stent or bypass operation when the FFR is less than 0.8.
260,000 coronary angiographies are performed each year in France, of which two-thirds do not
lead to an interventional procedure. CCTA coupled with an intelligent predictive analysis
system could reduce this rate of invasive examinations that do not require an interventional
procedure. Various decision support systems have been developed recently using AI methods,
either for stenosis assessment or for FFR estimation. Their overall sensitivity is
insufficient, mainly because their training base is small (<100 cases) and they have not been
validated in a multicenter setting. On the contrary, the radiology department of the IMM has
built a large base of images (n=5000) of CCTA from various machines, qualified by an expert
and associated with FFR values. This learning base feeding a deep learning system has very
good predictive performances of stenosis and FFR on a new test base of CCTA images alone.
Obtaining these 2 parameters in a single acquisition would enhance the radiologist's accuracy
and avoid the need for invasive FFR. It therefore seems appropriate to reinforce this system
with a multicenter feed and to perform an external validation on an independent sample.
OBJECTIVES Main : Predictive performance, at the coronary vessel level, of an intelligent
Coronary CT AI based image analysis system on the detection of a stenosis requiring
intervention, versus invasive coronary angiography with reference measurement (FFR).
Secondary:- predictive performance regarding the indication for intervention at the patient
level (i.e., the synthesis of all the assessments of his or her vessels) - medico-economic
analysis of the cost-effectiveness type comparing two diagnostic strategies (CCTA+AI, vs.
usual care = CCTA + invasive FFR) in terms of effectiveness (shortening of the time to obtain
treatment, unnecessary invasive coronary angiography avoided, complications avoided), cost
and incremental cost-effectiveness ratio
JUDGEMENT CRITERIA Primary: This criterion is calculated on the validation sample.
Sensitivity at the vessel level will be calculated as the ratio of the number of stenotic
vessels classified as interventional by the AI system to the total number of stenotic vessels
classified as interventional by the reference method. The other metrics (specificity,
likelihood ratios, prevalence and predictive errors) will be calculated, all with their 95%
confidence intervals.
Secondary:- Predictive performance regarding the indication of intervention at the patient
level: sensitivity, specificity and other metrics- Cost per complication avoided. It will be
calculated from the Differential Cost Outcome Ratio (DCOR), which is the difference in costs
(from a Medicare perspective) divided by the difference in the number of coronary
complications between the two strategies studied, and will be supplemented by sensitivity
analyses.
METHODOLOGY A multicenter study that will collect CCTA images and invasive FFR measurements
from consecutive patients under standardized conditions. The total sample will be randomly
partitioned into a learning sample representing approximately 60% of the population and a
validation sample (40%). The reference results will be obtained:- for the % of stenosis, at
the vessel level: by consensus of independent experts (Delphi method on dedicated WWW site)
on an a posteriori examination of the images (vessel, anonymized, blinded to the local
interpretation and FFR) - for FFR at the vessel level: by a standardized invasive procedure
performed as soon as stenosis is ≥40% according to the local radiologist's estimation; the
result is first quantitative and then dichotomized at the FFR threshold ≤0.8- for patient
classification (indication for stenting/bypassing or not) by the conjunction of reference
results obtained vessel by vessel: indication for stenting/trimming if at least one vessel
has an FFR≤0.8; no indication if no vessel has stenosis ≥ CAD-RADS 3 (≥50%) or otherwise has
an FFR value ≤0.8
ELIGIBILITY CRITERIA- Adult patient,- with no diagnosed coronary status or history of
stenting or bypass surgery- whose CCTA evaluation by the local radiologist results in at
least an intermediate stenosis ≥40% on at least one vessel with indication for FFR
measurement.- Who has not expressed opposition to the use of their data.
RESEARCH SCHEME 11 participating centers
NUMBER OF SUBJECTS A minimum is a sensitivity of 95% on the test basis. To estimate this
parameter with an accuracy of +-2.5% (92.5%-97.5%), with a 5% two-sided risk of error, 300
observations (at the vessel level) are required, that is, at a rate of approximately 1.5
vessels with lesions per patient, 200 patients with an indication for intervention. Knowing
that 2/3 of the FFR will be negative, the number of new patients with an FFR is 600 and
taking into account 10% of uninterpretable images, 670 new patients for the test base (40% of
the total). The number of patients for the learning base (60%) must be 1000. This means a
total recruitment of 1670 patients. 340 patients for the learning base will be included
retrospectively and the remaining 1330 patients to complete the learning base and the
validation base will be included prospectively.
RESEARCH QUALIFICATION
Category 3 research involving the human person:
For patients who will be included in the retrospective part: only their data from their
medical records will be used.
Patients who will be included in the prospective part will additionally complete the EQ5D5L
questionnaire before coronary angiography and at the end of the patient's participation (4
months after the CCTA).
STUDY TIME FRAME Patient participation time: 4 months Entry time: 2 years
