Coronary Artery Disease
Conditions
Brief summary
The objective of the PLATFORM Study is to compare clinical outcomes, resource utilization, and quality of life (QOL) of FFRCT-guided evaluation versus standard practice evaluation in patients with suspected CAD in order to further inform patients, health care providers, and other stakeholders about which technologies are most effective and efficient in the diagnosis of CAD
Detailed description
The OVERALL OBJECTVE of this post-market, multicenter, longitudinal, prospective, consecutive cohort study is to compare clinical outcomes, resource utilization, and quality of life (QOL) in subjects receiving standard practice evaluation and treatment versus subjects receiving FFRCT-guided evaluation and treatment in subjects with suspected CAD in order to further inform patients, health care providers, and other stakeholders about which technologies are most effective and efficient in the diagnosis of CAD. Cohort 1 of this study will assess outcomes incorporating standard practice evaluation and Cohort 2 will assess outcomes incorporating FFRCT-guided evaluation. Each Cohort will be further delineated based upon initial presentation, whereas subjects presenting for initial non-invasive testing will be designated as Cohorts 1A and 2A; and subjects already referred for ICA will be designated as Cohorts 1B and 2B. SPECIFIC OBJECTIVES for sequential cohort comparisons: 1. To compare the rate of ICA documenting non-obstructive coronary artery disease, clinical outcomes, and QOL following standard practice for diagnostic and treatment planning modalities in Cohort 1 versus incorporating FFRCT as the preferred test to guide further invasive management and medical treatment in Cohort 2; 2. To compare resource utilization following standard practice for diagnostic and treatment pathways in Cohort 1 versus incorporating FFRCT as the preferred test to guide further invasive management and medical treatment in Cohort 2; 3. To provide supporting data for generating new guidelines for diagnosis and prognosis of CAD with comparative analysis of the risk stratification with the Updated Diamond-Forrester risk model (UDF); 4. To provide society including patients, health care providers and other stakeholders with information about which diagnostic technologies are most effective and efficient in managing patients with CAD.
Interventions
None listed
Sponsors
Duke Clinical Research Institute
HeartFlow, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>18 years * Providing written informed consent * Subjects with intermediate likelihood of obstructive CAD with an Updated Diamond-Forrester (UDF) risk score 20-80% with symptomatic, suspected CAD who: * In Cohort 1A & 2A only are scheduled to undergo initial clinically-indicated non-invasive coronary evaluation, and have not undergone non-invasive coronary evaluation, including exercise tolerance testing, stress echocardiography, SPECT or MRI, or cCTA, within the past 90 days OR ICA at any time; or * In Cohort 1B & 2B only have been referred to invasive coronary angiography (ICA) and have not undergone ICA within the past 90 days * Ability to undergo cCTA
Exclusion criteria
* Suspicion of acute coronary syndrome. Subjects experiencing unstable angina are not excluded where clinical documentation has ruled out a myocardial infarction. * Prior, clinically documented myocardial infarction * PCI prior to first test * CABG prior to first test * Contraindications for cCTA such as: * Presence of pacemaker or internal defibrillator leads * Atrial Fibrillation * Known anaphylactic allergy to iodinated contrast * Pregnancy or unknown pregnancy status in women of childbearing potential * Body mass index \>35 kg/m2 * Contraindication to acute beta blockade * Contraindication to acute sublingual nitrate administration * Prosthetic heart valve * Contraindications to FFRCT * Complex Congenital Heart disease other than anomalous coronary origins alone * Ventricular septal defect with known Qp/Qs\>1.4 * Requiring an emergent procedure within 48 hours of presentation * Evidence of active clinical instability, including cardiogenic shock, unstable blood pressure with systolic blood pressure \<90 mmHg, or NYHA Grade III or IV congestive heart failure or acute pulmonary edema * Any active, serious, life-threatening disease with a life expectancy of less than 2 years * Inability to comply with study follow-up requirements * Current participation in any other clinical trial involving an investigational device or dictating care pathways at the time of enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Negative Invasive Coronary Angiography | 90 Days from first test | The primary endpoint of the PLATFORM Study is 90 day (+30/-15 days) rate of coronary angiogram showing no stenosis \> 50% in a vessel \> 2.0 mm by Quantitative Coronary Angiography (QCA), or no invasively-measured FFR \< 0.80 in a segment distal to a stenosis in a vessel \> 2.0 mm by QCA between Cohort 1 and 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of MACE | 90 days from first test | 90 days (+30/-30 days) Cohort 1 and Cohort 2 Major Adverse Coronary Event (MACE) rates, defined as: 1. All cause death 2. Non-fatal MI 3. Unplanned hospitalization for acute coronary syndrome (ACS) leading to urgent revascularization |
| Number of MACE or Vascular Complications | 90 days from first test | 90 days (+30/-30 days) Major Adverse Coronary Event (MACE) rates, defined as: all cause death, non-fatal MI, unplanned hospitalization for acute coronary syndrome (ACS) leading to urgent revascularization and vascular complications (related to any coronary testing or procedure).This secondary endpoint compared the rates of MACE and vascular events across all subjects in Cohort 1 vs Cohort 2, Cohort 1A vs Cohort 2A and Cohort 1B vs Cohort 2B. The rates of MACE and vascular events were calculated by dividing the number of subjects with MACE and vascular events by the total number of subjects assigned to each analysis population. |
| Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | 90 days from first test | Comparison of Resource utilization between cohort 1 and cohort 2 at 90 days (+/- 30 days): 1. Non-invasive diagnostic tests 2. Invasive diagnostic tests 3. Coronary revascularization procedures |
| Number of Participants With Medications Used by Type | at 90 days | Comparison of medication use between cohort 1A, 1B and cohort 2A, 2B at 90 days (+/- 15 days) |
Countries
Austria, Belgium, Denmark, France, Germany, Italy, United Kingdom, United States
Participant flow
Recruitment details
Subjects will be referred for non-invasive and/or invasive testing and evaluation. Prior to treatment of each subject considered for percutaneous coronary intervention (PCI) and/or coronary artery bypass grafting (CABG), the investigator and the institution's heart team will review clinical data and results of the diagnostic tests to recommend a treatment strategy, according to the institution's standard practice.
Pre-assignment details
Patients were eligible for enrollment if they were symptomatic, had an intermediate likelihood of CAD, did not have an established diagnosis of CAD, and were referred for clinically indicated testing to evaluate CAD. Patients referred for noninvasive testing were enrolled in a separate stratum than patients referred for invasive testing. The choice to refer the patient for invasive testing rather than noninvasive testing was made by the local clinicians before enrollment in the study.
Participants by arm
| Arm | Count |
|---|---|
| Invasive Cohort (Cohort 1) Usual Care (Cohort 1) of the study is an observational evaluation of resource utilization and outcomes based on standard practice for diagnosis and treatment of subjects with symptomatic suspected CAD and intermediate likelihood of obstructive CAD. | 187 |
| Invasive Cohort (Cohort 1) FFRCT The second cohort of patients, enrolled after completion of the enrollment of the first cohort, was evaluated by CTA, with determination of FFRCT when a lesion of $30% stenosis was detected, or the patient was referred to invasive angiography. | 193 |
| Non-invasive (Cohort 2) Usual Care (Cohort 2) Subjects will be referred for non-invasive and/or invasive testing and evaluation. Prior to treatment of subjects considered for PCI and/or CABG, the investigator and the institution's heart team will review the results of all available diagnostic tests, including cCTA and FFRCT, and will recommend a treatment strategy accordingly. | 100 |
| Non-invasive Cohort (Cohort 2) FFRCT The second cohort of patients, enrolled after completion of the enrollment of the first cohort, was evaluated by CTA, with determination of FFRCT when a lesion of $30% stenosis was detected, or the patient was referred to invasive angiography. | 104 |
| Total | 584 |
Baseline characteristics
| Characteristic | Invasive Cohort (Cohort 1) Usual Care | Invasive Cohort (Cohort 1) FFRCT | Non-invasive (Cohort 2) Usual Care | Non-invasive Cohort (Cohort 2) FFRCT | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.36 years STANDARD_DEVIATION 10.93 | 60.72 years STANDARD_DEVIATION 10.2 | 57.91 years STANDARD_DEVIATION 10.72 | 59.48 years STANDARD_DEVIATION 9.33 | 60.86 years STANDARD_DEVIATION 10.54 |
| Atypical angina | 122 Participants | 142 Participants | 91 Participants | 80 Participants | 435 Participants |
| Current smoker | 42 Participants | 38 Participants | 22 Participants | 23 Participants | 125 Participants |
| Diabetes | 36 Participants | 30 Participants | 8 Participants | 6 Participants | 80 Participants |
| Hyperlipidemia | 76 Participants | 77 Participants | 22 Participants | 28 Participants | 203 Participants |
| Hypertension | 111 Participants | 111 Participants | 38 Participants | 57 Participants | 317 Participants |
| Pre-test probability of CAD | 97 Participants | 95 Participants | 56 Participants | 47 Participants | 295 Participants |
| Prior noninvasive testing | 92 Participants | 100 Participants | 0 Participants | 5 Participants | 197 Participants |
| Sex: Female, Male Female | 79 Participants | 74 Participants | 34 Participants | 44 Participants | 231 Participants |
| Sex: Female, Male Male | 108 Participants | 119 Participants | 66 Participants | 60 Participants | 353 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 100 | 0 / 104 | 1 / 187 | 0 / 193 |
| other Total, other adverse events | 6 / 100 | 13 / 104 | 137 / 187 | 24 / 193 |
| serious Total, serious adverse events | 2 / 100 | 1 / 104 | 6 / 187 | 9 / 193 |
Outcome results
Primary
Number of Participants With Negative Invasive Coronary Angiography
The primary endpoint of the PLATFORM Study is 90 day (+30/-15 days) rate of coronary angiogram showing no stenosis \> 50% in a vessel \> 2.0 mm by Quantitative Coronary Angiography (QCA), or no invasively-measured FFR \< 0.80 in a segment distal to a stenosis in a vessel \> 2.0 mm by QCA between Cohort 1 and 2.
Time frame: 90 Days from first test
Population: ICA - Invasive coronary angiography. Independent core laboratories performed quantitative coronary angiography.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of Participants With Negative Invasive Coronary Angiography | 137 Participants |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of Participants With Negative Invasive Coronary Angiography | 24 Participants |
Secondary
Number of MACE
90 days (+30/-30 days) Cohort 1 and Cohort 2 Major Adverse Coronary Event (MACE) rates, defined as: 1. All cause death 2. Non-fatal MI 3. Unplanned hospitalization for acute coronary syndrome (ACS) leading to urgent revascularization
Time frame: 90 days from first test
Population: The analysis population was defined as all subjects who were enrolled into the study. Safety was monitored throughout the study. The low number of MACE events made it impossible to analyze the powered secondary endpoint. None of the events were related to the FFRCT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of MACE | 1 Participants |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of MACE | 0 Participants |
| Invasive Cohort (Cohort 1) Usual Care | Number of MACE | 2 Participants |
| Invasive Cohort (Cohort 1) FFRCT | Number of MACE | 2 Participants |
Secondary
Number of MACE or Vascular Complications
90 days (+30/-30 days) Major Adverse Coronary Event (MACE) rates, defined as: all cause death, non-fatal MI, unplanned hospitalization for acute coronary syndrome (ACS) leading to urgent revascularization and vascular complications (related to any coronary testing or procedure).This secondary endpoint compared the rates of MACE and vascular events across all subjects in Cohort 1 vs Cohort 2, Cohort 1A vs Cohort 2A and Cohort 1B vs Cohort 2B. The rates of MACE and vascular events were calculated by dividing the number of subjects with MACE and vascular events by the total number of subjects assigned to each analysis population.
Time frame: 90 days from first test
Population: The analysis population was defined as all subjects who were enrolled into the study. It is important to note that none of the adverse events reported throughout the study were related to FFRCT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of MACE or Vascular Complications | 0 Participants |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of MACE or Vascular Complications | 1 Participants |
| Invasive Cohort (Cohort 1) Usual Care | Number of MACE or Vascular Complications | 2 Participants |
| Invasive Cohort (Cohort 1) FFRCT | Number of MACE or Vascular Complications | 7 Participants |
Secondary
Number of Participants With Medications Used by Type
Comparison of medication use between cohort 1A, 1B and cohort 2A, 2B at 90 days (+/- 15 days)
Time frame: at 90 days
Population: Values are the total number of patients who used particular medication (multiple medication types might be used per each patient)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of Participants With Medications Used by Type | Aspirin | 29 participants (total count) |
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of Participants With Medications Used by Type | Statin | 24 participants (total count) |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of Participants With Medications Used by Type | Statin | 29 participants (total count) |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of Participants With Medications Used by Type | Aspirin | 45 participants (total count) |
| Invasive Cohort (Cohort 1) Usual Care | Number of Participants With Medications Used by Type | Aspirin | 115 participants (total count) |
| Invasive Cohort (Cohort 1) Usual Care | Number of Participants With Medications Used by Type | Statin | 83 participants (total count) |
| Invasive Cohort (Cohort 1) FFRCT | Number of Participants With Medications Used by Type | Aspirin | 90 participants (total count) |
| Invasive Cohort (Cohort 1) FFRCT | Number of Participants With Medications Used by Type | Statin | 77 participants (total count) |
Secondary
Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days
Comparison of Resource utilization between cohort 1 and cohort 2 at 90 days (+/- 30 days): 1. Non-invasive diagnostic tests 2. Invasive diagnostic tests 3. Coronary revascularization procedures
Time frame: 90 days from first test
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | cCTA without FFRCT | 8 Participants |
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | Stress Echo | 2 Participants |
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | cCTA with FFRCT | 0 Participants |
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | Nuclear/Stress MPI/CMR | 3 Participants |
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | ICA | 12 Participants |
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | CABG | 2 Participants |
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | IVUS, OCT, or FFR | 3 Participants |
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | PCI | 3 Participants |
| Planned Invasive Test Usual Care Strategy (Cohort 1B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | ECG | 2 Participants |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | cCTA without FFRCT | 2 Participants |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | ICA | 19 Participants |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | ECG | 3 Participants |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | CABG | 1 Participants |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | Stress Echo | 0 Participants |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | Nuclear/Stress MPI/CMR | 2 Participants |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | cCTA with FFRCT | 17 Participants |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | PCI | 9 Participants |
| Planned Invasive Test FFRCT Guided Strategy (Cohort 2B) | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | IVUS, OCT, or FFR | 7 Participants |
| Invasive Cohort (Cohort 1) Usual Care | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | CABG | 17 Participants |
| Invasive Cohort (Cohort 1) Usual Care | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | ECG | 59 Participants |
| Invasive Cohort (Cohort 1) Usual Care | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | PCI | 42 Participants |
| Invasive Cohort (Cohort 1) Usual Care | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | cCTA with FFRCT | 0 Participants |
| Invasive Cohort (Cohort 1) Usual Care | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | IVUS, OCT, or FFR | 17 Participants |
| Invasive Cohort (Cohort 1) Usual Care | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | Stress Echo | 7 Participants |
| Invasive Cohort (Cohort 1) Usual Care | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | ICA | 187 Participants |
| Invasive Cohort (Cohort 1) Usual Care | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | Nuclear/Stress MPI/CMR | 23 Participants |
| Invasive Cohort (Cohort 1) Usual Care | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | cCTA without FFRCT | 21 Participants |
| Invasive Cohort (Cohort 1) FFRCT | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | CABG | 10 Participants |
| Invasive Cohort (Cohort 1) FFRCT | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | Nuclear/Stress MPI/CMR | 5 Participants |
| Invasive Cohort (Cohort 1) FFRCT | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | ECG | 32 Participants |
| Invasive Cohort (Cohort 1) FFRCT | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | Stress Echo | 6 Participants |
| Invasive Cohort (Cohort 1) FFRCT | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | cCTA without FFRCT | 12 Participants |
| Invasive Cohort (Cohort 1) FFRCT | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | cCTA with FFRCT | 64 Participants |
| Invasive Cohort (Cohort 1) FFRCT | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | IVUS, OCT, or FFR | 30 Participants |
| Invasive Cohort (Cohort 1) FFRCT | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | ICA | 76 Participants |
| Invasive Cohort (Cohort 1) FFRCT | Number of Participants With Resource (CV Test Types Performed) Utilization at 90 Days | PCI | 45 Participants |