Coronary Artery Disease
Conditions
Keywords
Coronary artery disease, Coronary computed tomographic angiography, Fractional flow reserve
Brief summary
The primary of this registry is to evaluate whether the availability of CTA/CT-FFR procedure could effectively optimize the flow of clinical practice of stable chest pain versus conventional clinical pathway in decision making, avoid the overuse of invasive procedure, finally improve clinical prognosis and reduce total medical expenditure. This registry is randomized, open labeled, prospective designed and will be performed in 6 Chinese hospitals. Approximately 1200 subjects will be enrolled and subsequently assigned to either routine clinically-indicated diagnostic care group (CID arm) or CTA/CT-FFR care group (CTA/CT-FFR arm) via computer-generated random numbers (1:1 ratio)
Detailed description
Based on the clinical fact that less stress myocardial perfusion scan are performed rather than stress exercise electrocardiogram (ECG) in China, more patients undergo coronary computed tomographic angiography (CTA) for determining whether they should be sent to catheter lab. However, nearly 30% of patients sent to catheter lab were found without obstructive coronary artery disease (CAD) and this invasive procedure was unnecessary and overused partly. Fortunately, fractional flow reserve (FFR) based non-invasive CT algorithm technology (CT-FFR) showed a great potential in detecting functional myocardial ischemia related to coronary specific lesion (Discovery-Flow, DEFACTO and NXT trial)\[1-3\]. Moreover, clinical care guided by CT-FFR could provide benefits with equivalent clinical outcomes and lower expenditure, compared with routine clinical care over 1-year follow-up (Platform trial). On the other aspect, ADVANCE trial revealed that CT-FFR modified treatment recommendation was associated with less negative invasive coronary angiography (ICA), predicted revascularization and identified subjects at low risk of adverse events through 90 days in real-world. However, these studies was not randomized designed and selection bias still existed. So our trial aims to evaluate whether CTA/CT-FFR outperforms the regular diagnostic care in ruling out patients without significantly obstructive CAD before catheter lab and improving clinical prognosis during follow-up in a randomized design.
Interventions
DIAGNOSTIC_TESTCT-FFR assessment
When subjects are randomized to the CTA/CT-FFR arm, FFR based on the coronary CTA imaging will be measured. DEEPVESSEL FFR workstation is very dedicated software utilizing the original CTA imaging to meter simulated FFR values based on a machine learning algorithm. The first step is to extract a 3D coronary artery model and generate coronary centerlines which are similar to the routine reconstruction of coronary CTA. The centerlines are extracted using a minimal path extraction filter. Then a novel path-based deep learning model, referred to DEEPVESSEL FFR, is used to predict the simulated FFR values on the vascular centerlines. Deep learning algorithm is used to establish characteristic sample database of coronary hemodynamics characteristic parameters. When deep training model is proved to be valid, it is applied to a new lesion-specific measurement. Lesion-specific CT-FFR is defined as simulated FFR value at distance of 20mm away from the lesion of interest.
Sponsors
Beijing Anzhen Hospital
First Affiliated Hospital of Xinjiang Medical University
Qilu Hospital of Shandong University
Second Affiliated Hospital, School of Medicine, Zhejiang University
Tongji Hospital
Chinese PLA General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* New-onset chest pain suspicious for CAD * Coronary CTA result showed that the diameter stenosis is between 30 and 90% in at least one major coronary artery (coronary artery diameter ≥ 2.5 mm) * Intermediate-to-high pretest probability of CAD based on CAD Consortium Score * No prior evaluation for this episode of symptoms * Agree to participate in this clinical study and sign written informed consent
Exclusion criteria
* Diagnosed or suspected acute coronary syndrome requiring hospitalization or emergent testing * Hemodynamically or clinically unstable condition systolic blood pressure \< 90 mmHg or serious atrial or ventricular arrhythmias * Known CAD with prior myocardial infarction, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or any angiographic evidence of ≥ 50% stenosis in any major coronary artery * Patients with left main branch stenosis ≥ 50% or major coronary artery stenosis \> 90% * Known severe congenital, valvular (moderate and above), or cardiomyopathy process (hypertrophic cardiomyopathy or reduced systolic left ventricular function ≤ 40%) which could explain cardiac symptoms * Unable to provide written informed consent or participate in long-term follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With ICA Without Obstructive CAD or Intervention | 90 days | Number of those patients with planned ICA in whom no significant obstructive CAD (no stenosis≥70% by core lab quantitative analysis or invasive FFR≤0.8) is found or interventions (including stent implantation, balloon dilation and bypass graft) are performed during ICA within 90 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participant With Major Adverse Cardiovascular Event | 12 months | Major adverse cardiovascular event include death, myocardial infarction (MI), major complications from cardiovascular (CV) procedures or testing, and unstable angina hospitalization |
| Medical Expenditure | 12 months | Overall cardiac medical expenditure by intention to treat at both 90 days and 12 months cumulatively |
| Patient Reporting Outcomes | Study entry, 3 months, 6 months and12 months | Patient reporting outcomes as measured by Seattle Angina Questionnaire-7(SAQ-7) Scale, use SAQ-7-item instrument that measures patient reported symptoms, function and quality of life for subjects with CAD within 12 months. The SAQ-7 score is calculated as the average of the physical limitation score, quality of life score and angina frequency score. The physical limitation score, quality of life score and angina frequency score range from 0 to 100 each. Therefore, the SAQ-7 score also ranges from 0 to 100.The higher the SAQ-7 socre, physical limitation score, quality of life score and angina frequency score are, the better the quality of life for patients with angina. |
| Cumulative Radiation Exposure | 90 days, 12 months | Cumulative radiation exposure for any examination within 90 days and 12 months. Due to not enough data acquired, the investigators decided not to report at this time |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CTA/CT-FFR Care Group If the subjects are randomly allocated to CT-FFR arm, they will be examined by DeepFFR for three major epicardial arteries. If the result of CT-FFR calculation is less than or equal to 0.8 in one or more major，coronary arteries, the patient will be referred to ICA directly; if the result of CT-FFR value is more than 0.8, optimal medical therapy will be recommended. The decision on the mode of revascularization is left to the treating cardiologists and depends on local practice standard.
CT-FFR: DeepFFR workstation is very dedicated software utilizing the original CTA imaging to meter simulated FFR values in artificial intelligence model.The first step is to extract a 3D coronary artery model and generate coronary centerlines which are similar to the routine reconstruction of coronary CTA. The centerlines are extracted using a minimal path extraction filter. Then a novel path-based deep learning model, referred to DeepFFR, is used to predict the simulated FFR values on the vascular centerlines. Deep learning algorithm is used to establish characteristic sample database of coronary hemodynamics characteristic parameters. When deep training model is proved to be valid, it is applied to a new lesion-specific measurement. Lesion-specific CT-FFR is defined as simulated FFR value at distance of 20mm away from the lesion of interest. | 608 |
| Routine Clinically-indicated Diagnostic Care Group If the subjects are randomized to usual care arm, attending physicians will decide the next step of diagnosis and treatment, such as exercise ECG, stress cardiac echo, cardiac MR, and SPECT. According to the results of examination combined with risk factors assessment and clinical manifestations, physicians should provide recommendation whether the subjects would undergo ICA or not. | 608 |
| Total | 1,216 |
Baseline characteristics
| Characteristic | CTA/CT-FFR Care Group | Routine Clinically-indicated Diagnostic Care Group | Total |
|---|---|---|---|
| Age, Continuous | 60.0 years STANDARD_DEVIATION 8.3 | 59.2 years STANDARD_DEVIATION 11.5 | 59.6 years STANDARD_DEVIATION 10 |
| Body mass index | 25.1 kg/m² | 25.3 kg/m² | 25.2 kg/m² |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 210 Participants | 221 Participants | 431 Participants |
| Sex: Female, Male Male | 398 Participants | 387 Participants | 785 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 587 | 1 / 589 |
| other Total, other adverse events | 39 / 587 | 44 / 589 |
| serious Total, serious adverse events | 14 / 587 | 25 / 589 |
Outcome results
Primary
Number of Participants With ICA Without Obstructive CAD or Intervention
Number of those patients with planned ICA in whom no significant obstructive CAD (no stenosis≥70% by core lab quantitative analysis or invasive FFR≤0.8) is found or interventions (including stent implantation, balloon dilation and bypass graft) are performed during ICA within 90 days.
Time frame: 90 days
Population: In the general population, patients with severe coronary stenosis maybe considered to be sent to catheter room, while the main endpoint is the negative findings during angiography. Therefore, for instance, the total population in the CT-FFR group is 608 (row1), of which 421 patients (row2, 3) enter the catheter room for coronary angiography. Therefore, the proportion of the three rows is different.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CTA/CT-FFR Care Group | Number of Participants With ICA Without Obstructive CAD or Intervention | Number of patients undergoing ICA | 421 Participants |
| CTA/CT-FFR Care Group | Number of Participants With ICA Without Obstructive CAD or Intervention | Number of patients with ICA without obstructive CAD or intervention | 119 Participants |
| CTA/CT-FFR Care Group | Number of Participants With ICA Without Obstructive CAD or Intervention | Number of patients with ICA without obstructive CAD | 88 Participants |
| CTA/CT-FFR Care Group | Number of Participants With ICA Without Obstructive CAD or Intervention | Number of patients with ICA without intervention | 31 Participants |
| Routine Clinically-indicated Diagnostic Care Group | Number of Participants With ICA Without Obstructive CAD or Intervention | Number of patients with ICA without intervention | 39 Participants |
| Routine Clinically-indicated Diagnostic Care Group | Number of Participants With ICA Without Obstructive CAD or Intervention | Number of patients undergoing ICA | 483 Participants |
| Routine Clinically-indicated Diagnostic Care Group | Number of Participants With ICA Without Obstructive CAD or Intervention | Number of patients with ICA without obstructive CAD | 184 Participants |
| Routine Clinically-indicated Diagnostic Care Group | Number of Participants With ICA Without Obstructive CAD or Intervention | Number of patients with ICA without obstructive CAD or intervention | 223 Participants |
Comparison: Rate of ICA without obstructive CAD or intervention within 90 daysp-value: 0.05Chi-squared
Comparison: Rate of patients underwent revascularizationp-value: <0.001Chi-squared
Secondary
Cumulative Radiation Exposure
Cumulative radiation exposure for any examination within 90 days and 12 months. Due to not enough data acquired, the investigators decided not to report at this time
Time frame: 90 days, 12 months
Secondary
Medical Expenditure
Overall cardiac medical expenditure by intention to treat at both 90 days and 12 months cumulatively
Time frame: 12 months
Population: The primary endpoint analysis was performed in both groups as the primary endpoint was assessable at baseline. However, secondary endpoints were assessed after 1-year follow-up and due to loss to follow-up（21 in CT-FFR group; 19 in standard care group）, 587 and 589 patients from each group were available for final analysis of secondary endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CTA/CT-FFR Care Group | Medical Expenditure | 47032 ¥ | Standard Deviation 38533 |
| Routine Clinically-indicated Diagnostic Care Group | Medical Expenditure | 51265 ¥ | Standard Deviation 41462 |
p-value: 0.07Wilcoxon (Mann-Whitney)
Secondary
Number of Participant With Major Adverse Cardiovascular Event
Major adverse cardiovascular event include death, myocardial infarction (MI), major complications from cardiovascular (CV) procedures or testing, and unstable angina hospitalization
Time frame: 12 months
Population: The primary endpoint analysis was performed in both groups as the primary endpoint was assessable at baseline. However, secondary endpoints were assessed after 1-year follow-up and due to loss to follow-up（21 in CT-FFR group; 19 in standard care group）, 587 and 589 patients from each group were available for final analysis of secondary endpoints.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CTA/CT-FFR Care Group | Number of Participant With Major Adverse Cardiovascular Event | 48 Participants |
| Routine Clinically-indicated Diagnostic Care Group | Number of Participant With Major Adverse Cardiovascular Event | 54 Participants |
p-value: 0.895% CI: [0.59, 1.3]Regression, Cox
Secondary
Patient Reporting Outcomes
Patient reporting outcomes as measured by Seattle Angina Questionnaire-7(SAQ-7) Scale, use SAQ-7-item instrument that measures patient reported symptoms, function and quality of life for subjects with CAD within 12 months. The SAQ-7 score is calculated as the average of the physical limitation score, quality of life score and angina frequency score. The physical limitation score, quality of life score and angina frequency score range from 0 to 100 each. Therefore, the SAQ-7 score also ranges from 0 to 100.The higher the SAQ-7 socre, physical limitation score, quality of life score and angina frequency score are, the better the quality of life for patients with angina.
Time frame: Study entry, 3 months, 6 months and12 months
Population: The primary endpoint analysis was performed in both groups as the primary endpoint was assessable at baseline. However, secondary endpoints were assessed after 1-year follow-up and due to loss to follow-up（21 in CT-FFR group; 19 in standard care group）, 587 and 589 patients from each group were available for final analysis of secondary endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Quality of life score in 12 month | 87.1 scores on a scale | Standard Deviation 3 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Physical limitation score in 6 month | 81.1 scores on a scale | Standard Deviation 1.7 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Seattle Angina Questionnaire-7(SAQ-7) Scale in 6 month | 81.4 scores on a scale | Standard Deviation 1.3 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Physical limitation score in 12 month | 88.9 scores on a scale | Standard Deviation 3.3 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Seattle Angina Questionnaire-7(SAQ-7) Scale in study entry | 57.6 scores on a scale | Standard Deviation 4.5 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Quality of life score in study entry | 61.2 scores on a scale | Standard Deviation 4.7 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Seattle Angina Questionnaire-7(SAQ-7) Scale in 12 month | 86.3 scores on a scale | Standard Deviation 3.1 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Quality of life score in 3 month | 77.1 scores on a scale | Standard Deviation 1.8 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Angina frequency score in study entry | 52.5 scores on a scale | Standard Deviation 4.5 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Quality of life score in 6 month | 82 scores on a scale | Standard Deviation 1.9 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Angina frequency score in 3 month | 71.2 scores on a scale | Standard Deviation 1.9 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Physical limitation score in study entry | 59 scores on a scale | Standard Deviation 4.3 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Angina frequency score in 6 month | 81 scores on a scale | Standard Deviation 1.9 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Seattle Angina Questionnaire-7(SAQ-7) Scale in 3 month | 73.8 scores on a scale | Standard Deviation 1.1 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Angina frequency score in 12 month | 82.9 scores on a scale | Standard Deviation 3 |
| CTA/CT-FFR Care Group | Patient Reporting Outcomes | Physical limitation score in 3 month | 73 scores on a scale | Standard Deviation 1.1 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Angina frequency score in 12 month | 84.9 scores on a scale | Standard Deviation 2.4 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Quality of life score in 3 month | 75 scores on a scale | Standard Deviation 1.9 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Quality of life score in 6 month | 83 scores on a scale | Standard Deviation 1.7 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Seattle Angina Questionnaire-7(SAQ-7) Scale in study entry | 57.4 scores on a scale | Standard Deviation 4.3 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Seattle Angina Questionnaire-7(SAQ-7) Scale in 3 month | 72.3 scores on a scale | Standard Deviation 1 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Seattle Angina Questionnaire-7(SAQ-7) Scale in 6 month | 80.7 scores on a scale | Standard Deviation 1.2 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Seattle Angina Questionnaire-7(SAQ-7) Scale in 12 month | 87 scores on a scale | Standard Deviation 2.9 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Physical limitation score in study entry | 56.9 scores on a scale | Standard Deviation 4.1 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Physical limitation score in 3 month | 70.1 scores on a scale | Standard Deviation 0.9 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Physical limitation score in 6 month | 79.1 scores on a scale | Standard Deviation 1.9 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Physical limitation score in 12 month | 88 scores on a scale | Standard Deviation 2.9 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Quality of life score in study entry | 62.1 scores on a scale | Standard Deviation 4.7 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Angina frequency score in study entry | 53.2 scores on a scale | Standard Deviation 4.3 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Angina frequency score in 3 month | 72 scores on a scale | Standard Deviation 1.1 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Angina frequency score in 6 month | 80 scores on a scale | Standard Deviation 1.5 |
| Routine Clinically-indicated Diagnostic Care Group | Patient Reporting Outcomes | Quality of life score in 12 month | 88.2 scores on a scale | Standard Deviation 3.6 |
p-value: 0.15t-test, 2 sided