Coronary Artery DiseaseNCT03329469
The Value of CT-FFR Compared to CCTA or CCTA and Stress MPI in Low to Intermediate Risk ED Patients With Toshiba CT-FFR
An observational study of Coronary Artery Disease and Chest Pain, run by Northwell Health at 1 site in United States.
Trial summary
Coronary Computed Tomography Angiogram (CCTA) is a non-invasive imaging modality that has high sensitivity and negative predictive value for the detection of coronary artery disease (CAD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Chest Pain, Acute Coronary Syndrome
- What is being tested?
- Toshiba CT-FFR
- Type of treatment
- Medical device
- How many people
- 1,142 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Apr 2018to 31 Mar 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Low to intermediate risk chest pain patients (as defined by the criteria above presenting to North Shore University Hospital, Northwell Health, Manhasset, NY for emergent assessement of chest pain symptoms.
Who may be able to join
- Capable of giving informed consent.
- Able to cooperate with the technician performing the procedure.
- Patient must have Body Mass Index (BMI) <= 50.
- Patients must have non-ST Elevation Myocardial Infarction (STEMI) Electrocardiogram (EKG) without acute changes.
- Patients must present to North Shore University Hospital ED with Acute Chest Pain and require evaluation of coronary stenosis for the provisional diagnoses of acute chest pain or unstable angina or angina equivalent, and meet the criteria for CCTA by Heart Score Triage for the purpose of evaluation coronary stenosis for the provisional diagnoses of chest pain or angina or angina equivalent.
- 7.Patients must be able to take nitroglycerin and beta blockers. - 8.Patients must be 18 years of age or older.
Who cannot join
- Patients must not have a history of coronary stenting or coronary artery bypass graft.
- Patients must not have severe or end stage renal disease as diagnosed as estimated glomerular filtration rate (eGFR)<50.
- Patients must not have a BMI>50.
- Patient must not have any allergies to contrast.
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
North Shore University Hospital
Manhasset, New York, 11030
About this study
Official title: The Value of Fractional Flow Reserve Derived From Coronary CT Angiography as Compared to CCTA or CCTA and Stress MPI in the Triage of Low to Intermediate Emergent Chest Pain Patients With Toshiba CT-FFR
Coronary Computed Tomography Angiogram (CCTA) is a non-invasive imaging modality that has high sensitivity and negative predictive value for the detection of coronary artery disease (CAD). The main limitations of CCTA are its poor specificity and positive predictive value, as well as its inherent lack of physiologically relevant data on hemodynamic significance of coronary stenosis, a data that is provided either by non-invasive stress tests such as myocardial perfusion imaging (MPI) or invasively by measurement of the Fractional Flow Reserve (FFR). Recent advances in computational fluid dynamic techniques applied to standard CCTA are now emerging as powerful tools for virtual measurement of FFR from CCTA imaging (CT-FFR). These techniques correlate well with invasively measured FFR [1-4]. The primary purpose of this study is to evaluate the incremental benefit CT-FFR as compared to CCTA in triaging chest pain patients in emergency settings who are found to have obstructive CAD upon CCTA (generally >= 30% stenosis). Invasive FFR and short term clinical outcomes (90 days) will be correlated with each diagnostic modality in order to evaluate positive and negative predictive value of each.
Patients will undergo a CCTA, as part of routine emergency care. If the patient consents to participate in the study, the CCTA study will be assessed by Toshiba Software, to provide a computerized FFR reading, based on the CCTA study. If the noninvasive FFR diagnosis indicates obstructive disease, the patient will undergo cardiac catheterization with invasive FFR.
As CCTA utilization increases, the need to train additional imaging specialists will increase. This study will assess the capability of FFR-CT to enhance performance on both negative and positive predictive value for less experienced readers by providing feedback based on CT-FFR evaluation. If the use of CT-FFR improves accuracy of CCTA, as compared to the gold standard, (Invasive FFR), use of CT-FFR can potentially enhance performance for less experienced readers.
Read the detailed description
Background:
Coronary Computed Tomography Angiogram (CCTA) is a non-invasive imaging modality that has high sensitivity and negative predictive value for the detection of coronary artery disease (CAD). The main limitations of CCTA are its poor specificity and positive predictive value, as well as its inherent lack of physiologically relevant data on hemodynamic significance of coronary stenosis, a data that is provided either by non-invasive stress tests such as myocardial perfusion imaging (MPI) or invasively by measurement of the Fractional Flow Reserve (FFR). Recent advances in computational fluid dynamic techniques applied to standard CCTA are now emerging as powerful tools for virtual measurement of FFR from CCTA imaging (CT-FFR). These techniques correlate well with invasively measured FFR [1-4]. The primary purpose of this study is to evaluate the incremental benefit CT-FFR as compared to CCTA in triaging chest pain patients in ED settings who are found to have obstructive CAD upon CCTA (generally > 30% and < 90% stenosis). Invasive FFR and short term clinical outcomes (90 days) will be correlated with each diagnostic modality in order to evaluate positive and negative predictive value of each when used incrementally with CCTA.
Investigational Agent:
CCTA is increasingly becoming a preferred non-invasive imaging modality because of its high sensitivity and negative predictive value for the detection of CAD. It has been shown to be a robust imaging modality for evaluation of chest pain, and is associated with decreased unnecessary hospital admission, length of stay, major adverse cardiovascular event rates, recidivism rates, and downstream resource utilization compared to standard evaluation [5]. While findings so far are highly suggestive of CCTA's significance as a gatekeeper for ICA by ruling out obstructive CAD, fewer than half of obstructive stenosis identified by CCTA are ischemia-causing, signifying its poor positive predictive value and inherent lack of physiological information [6-8]. Consequently, utilization of CCTA has not entirely averted need for downstream testing for functional assessment of CCTA-detected obstructive lesions either by stress testing or ICA. Recently a major treatment modality, associated with the use of CCTA, has become available that offers promise for improving positive predictive value and physiological relevant hemodynamic data. Advances in computational fluid dynamic techniques applied to standard CCTA are now emerging as a powerful tool for virtual measurement of FFR from CCTA imaging (CT-FFR). This technique correlates well with invasively measured FFR [1-4]. While HeartFlow, Inc. has established an FDA approved process to assess coronary artery flow using noninvasive CT-FFR, this data requires 24 to 48 hours for processing.
Toshiba CT-FFR processing is non-FDA approved. The analytic method for vessel evaluation differs from that used by HeartFlow. Currently Toshiba is operating studies at four organizations around the world to assess the product's performance. Recently, the company published results from a study conducted Australia that showed positive findings on a sample of 42 patients, with positive predictive value of 74% vs. 60%.[9] The technology was presented at European Society of Cardiology (ESC) by Dr. S. Seneviratne and at Radiological Society of North America (RSNA) and the American Heart Association (AHA). Using the technology for ED patients offers potential advantage over the HeartFlow process, because the turnaround time for the procedure is one to three hours. However, the early positive findings need to be validated with a more robust study.
Preclinical Data:
While few publications regarding the use of CT-FFR specifically address the cost of diagnostic work-up for obstructive disease, it is clear that the cost structure resulting from changes in diagnostic testing will also change. Deferral or avoidance of cardiac catheterization and nuclear stress testing will likely yield significant reductions in the cost of the diagnostic testing. In addition, because the results of the CT-FFR are available in the ED, CT-FFR has the potential to offer financial savings from reduced length of stay, while increasing patient satisfaction and reducing exposure to increased risk related to the emergency department environment.
Clinical Data to Date:
From 1/1/2009 to 3/31/2015 the investigative team introduced and operated a CCTA Chest Pain triage program for low to intermediate risk patients at Stony Brook University Hospital ED and non-emergency outpatient services, the only tertiary care hospital in Suffolk County, New York (NY). Concurrently, the investigators established a registry to monitor patient outcomes for all patients receiving CCTA at Stony Brook Medicine. The registry contained nearly 15,000 patient CCTA procedures. The major registry study established the effectiveness of CCTA as an imaging modality for evaluating ED chest pain in a cost efficient manner with a false negative rate less than 1% [5]. However, the registry reflects the poorer positive predictive values documented by other industry studies [6-8].
False positive workup results in the necessity of performing cardiac catheterization on patients at risk for obstructive disease based on assessment with current standard of care (combined screening with CCTA and stress MPI). Reduction in the rate of false positive testing would lead to reduction in risk from invasive procedures and radiation exposure to patients and reduced cost to the health care system.
Study Objectives:
The purpose of this study is to evaluate the incremental benefit of Fractional Flow Reserve derived from CCTA (FFR-CT) compared to invasive FFR as the gold standard for patients with obstructive disease (generally, >= 30% stenosis).
General Study Design:
This will be a prospective clinical trial designed to evaluate the incremental benefit of virtual FFR measured from CCTA, compared to invasive FFR and CCTA alone for the detection of flow-limiting coronary stenosis, as defined by invasive FFR <=0.8 and vessel diameter of >=2mm.
1,142 consecutive patients who present to North Shore University Hospital Emergency Department (ED) for CCTA due to chest pain or angina over a two year period and meeting the study inclusion criteria are eligible for the study (Figure 1). The investigators will employ CCTA-appropriateness criteria to ensure proper selection of patients, derived from the Appropriate Use Criteria for Cardiac Computed Tomography published in 2010 and jointly authored by multiple societies including American College of Cardiology Foundation (ACCF), Society of Cardiovascular Computed Tomography (SCCT), and American College of Radiology (ACR) [11]. FFR-CT measurements will be performed following CCTA scan acquisition on software developed by Toshiba America Medical Systems, Inc. All eligible patients will undergo 320-slice multi detector CCTA and CT-FFR measurements. The severity of the stenosis will be determined on site by level III CCTA readers.
Patients with borderline (50% - 70%) or positive CCTA (>70%) stenosis readings will undergo ICA with invasive FFR measurement in accordance with accepted guidelines and established practice standard. Those patients with invasively measured FFR<=0.8 and with vessel diameter of >= 2mm, or those who require revascularizations based on invasively estimated stenosis severity (for patients who are totally obstructed) will be considered to have flow-limiting obstructive CAD, while the rest will be considered to have non-flow limiting obstructive CAD (if also >50% stenosis on ICA). If stenosis severity turns out to be < 50% after ICA, these patients will have been shown to have non-obstructive CAD. (Figure 1). Patients with 30% to 49% obstructive stenosis by CCTA standards and with positive CT-FFR, will also undergo invasive FFR and follow the protocol for those with > 50% obstruction. Patients with 0 to 49% obstructive disease and negative CT-FFR will be referred to optimal follow up care only.
- Being tested
- Toshiba CT-FFR
- Keywords
- Computed Tomography Fractional Flow Reserve (CT-FFR),, Computed Coronary Tomography Angiography (CCTA), Invasive Fractional Flow Reserve (iFFR), Fractional Flow Reserve (FFR), Emergency Department (ED), Emergency Room (ER)
- Medical subject headings
- Coronary Artery Disease, Chest Pain, Acute Coronary Syndrome, Emergencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Toshiba CT-FFRDevice
Also called Noninvasive CT-FFR, FFR-CT, Noninvasive FFR-CT
Patients receiving CCTA to diagnose acute chest pain or unstable angina will receive CT-FFR to estimate rate of blood flow through the coronary arteries. The rate of flow will be compared to the rate found on Invasive FFR (the gold standard) if the subject receives invasive FFR.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: 1: Toshiba CT-FFR Arm | All patients who consent will receive Toshiba CT-FFR and medically acceptable care based on the study protocol, commonly accepted standards of care, and the patients condition. Receives: Device: Toshiba CT-FFR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of CT-FFR to Invasive FFR
To evaluate sensitivity, specificity, positive and negative predictive value for CT-FFR, compared to invasive FFR.
Measured: Up to 2 years from the study initiation will be required to enroll all study patients and obtain invasive and noninvasive FFR.
Secondary outcomes (2)
Return Visits
To identify factors influencing return visits within 90 days for patient who had negative CCTA or Cardiac Catheterization findings.
Measured: Up to 27 months will be required to collect 90 day follow up information on all study participants.
Economic Impact
To Compare the cost of care using CT-FFR by evaluating potentially avoidable workup with stress testing and invasive FFR.
Measured: Up to 27 months will be requires to collect medical utilization after having administered CT-FFR
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start18 Apr 2018
- Primary completion31 Mar 2024 (estimated)
- Study completion31 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 1,142 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Collaborators
- Toshiba America Medical Systems, Inc.
- Responsible party
- Principal investigator, Michael Poon, Northwell Health
- Investigators
- Michael Poon, MD, Principal investigator, Northwell HealthShahryar Saba, MD, Study director, Northwell HealthAmar Shah, MD, Study director, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03329469
- Sponsor's protocol ID
- Northwell IRB #17-0187
- Status last verified
- Apr 2023
- First submitted
- 30 Oct 2017
- Last updated
- 10 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: No Individual Participant Data (IPD) will be shared with other researchers. All study data will be deidentified to protect individual study participants identity.
Publications
Min JK, Leipsic J, Pencina MJ, Berman DS, Koo BK, van Mieghem C, Erglis A, Lin FY, Dunning AM, Apruzzese P, Budoff MJ, Cole JH, Jaffer FA, Leon MB, Malpeso J, Mancini GB, Park SJ, Schwartz RS, Shaw LJ, Mauri L. Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. JAMA. 2012 Sep 26;308(12):1237-45. doi: 10.1001/2012.jama.11274.
PubMed 22922562Norgaard BL, Leipsic J, Gaur S, Seneviratne S, Ko BS, Ito H, Jensen JM, Mauri L, De Bruyne B, Bezerra H, Osawa K, Marwan M, Naber C, Erglis A, Park SJ, Christiansen EH, Kaltoft A, Lassen JF, Botker HE, Achenbach S; NXT Trial Study Group. Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). J Am Coll Cardiol. 2014 Apr 1;63(12):1145-1155. doi: 10.1016/j.jacc.2013.11.043. Epub 2014 Jan 30.
PubMed 24486266Ko BS, Cameron JD, Meredith IT, Leung M, Antonis PR, Nasis A, Crossett M, Hope SA, Lehman SJ, Troupis J, DeFrance T, Seneviratne SK. Computed tomography stress myocardial perfusion imaging in patients considered for revascularization: a comparison with fractional flow reserve. Eur Heart J. 2012 Jan;33(1):67-77. doi: 10.1093/eurheartj/ehr268. Epub 2011 Aug 2.
PubMed 21810860Niska R, Bhuiya F, Xu J. National Hospital Ambulatory Medical Care Survey: 2007 emergency department summary. Natl Health Stat Report. 2010 Aug 6;(26):1-31.
PubMed 20726217Poon M, Cortegiano M, Abramowicz AJ, Hines M, Singer AJ, Henry MC, Viccellio P, Hellinger JC, Ferraro S, Poon A, Raff GL, Voros S, Farkouh ME, Noack P. Associations between routine coronary computed tomographic angiography and reduced unnecessary hospital admissions, length of stay, recidivism rates, and invasive coronary angiography in the emergency department triage of chest pain. J Am Coll Cardiol. 2013 Aug 6;62(6):543-52. doi: 10.1016/j.jacc.2013.04.040. Epub 2013 May 15.
PubMed 23684682Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, Scherer M, Bellinger R, Martin A, Benton R, Delago A, Min JK. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008 Nov 18;52(21):1724-32. doi: 10.1016/j.jacc.2008.07.031.
PubMed 19007693Meijboom WB, Meijs MF, Schuijf JD, Cramer MJ, Mollet NR, van Mieghem CA, Nieman K, van Werkhoven JM, Pundziute G, Weustink AC, de Vos AM, Pugliese F, Rensing B, Jukema JW, Bax JJ, Prokop M, Doevendans PA, Hunink MG, Krestin GP, de Feyter PJ. Diagnostic accuracy of 64-slice computed tomography coronary angiography: a prospective, multicenter, multivendor study. J Am Coll Cardiol. 2008 Dec 16;52(25):2135-44. doi: 10.1016/j.jacc.2008.08.058.
PubMed 19095130Ko BS, Cameron JD, Munnur RK, Wong DTL, Fujisawa Y, Sakaguchi T, Hirohata K, Hislop-Jambrich J, Fujimoto S, Takamura K, Crossett M, Leung M, Kuganesan A, Malaiapan Y, Nasis A, Troupis J, Meredith IT, Seneviratne SK. Noninvasive CT-Derived FFR Based on Structural and Fluid Analysis: A Comparison With Invasive FFR for Detection of Functionally Significant Stenosis. JACC Cardiovasc Imaging. 2017 Jun;10(6):663-673. doi: 10.1016/j.jcmg.2016.07.005. Epub 2016 Oct 19.
PubMed 27771399Miller JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, Paul N, Clouse ME, Shapiro EP, Hoe J, Lardo AC, Bush DE, de Roos A, Cox C, Brinker J, Lima JA. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med. 2008 Nov 27;359(22):2324-36. doi: 10.1056/NEJMoa0806576.
PubMed 19038879Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P, Rubin GD; American College of Cardiology Foundation Appropriate Use Criteria Task Force; Society of Cardiovascular Computed Tomography; American College of Radiology; American Heart Association; American Society of Echocardiography; American Society of Nuclear Cardiology; North American Society for Cardiovascular Imaging; Society for Cardiovascular Angiography and Interventions; Society for Cardiovascular Magnetic Resonance; Kramer CM, Berman D, Brown A, Chaudhry FA, Cury RC, Desai MY, Einstein AJ, Gomes AS, Harrington R, Hoffmann U, Khare R, Lesser J, McGann C, Rosenberg A, Schwartz R, Shelton M, Smetana GW, Smith SC Jr. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. J Am Coll Cardiol. 2010 Nov 23;56(22):1864-94. doi: 10.1016/j.jacc.2010.07.005.
PubMed 21087721Koo BK, Erglis A, Doh JH, Daniels DV, Jegere S, Kim HS, Dunning A, DeFrance T, Lansky A, Leipsic J, Min JK. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study. J Am Coll Cardiol. 2011 Nov 1;58(19):1989-97. doi: 10.1016/j.jacc.2011.06.066.
PubMed 22032711
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Value of Fractional Flow Reserve Derived From Coronary CT Angiography as Compared to CCTA or CCTA and Stress MPI in the Triage of Low to Intermediate Emergent Chest Pain Patients With Toshiba CT-FFR
- ClinicalTrials.gov ID
- NCT03329469
- Acronym / sponsor ID
- Northwell IRB #17-0187
- Keywords
- Computed Tomography Fractional Flow Reserve (CT-FFR),, Computed Coronary Tomography Angiography (CCTA), Invasive Fractional Flow Reserve (iFFR), Fractional Flow Reserve (FFR), Emergency Department (ED), Emergency Room (ER)
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,142 participants (estimated)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Collaborators
- Toshiba America Medical Systems, Inc.
- Study start
- 18 Apr 2018 (actual)
- Primary completion
- 31 Mar 2024 (estimated)
- Study completion
- 31 Mar 2024 (estimated)
- First posted
- 6 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Coronary Computed Tomography Angiogram (CCTA) is a non-invasive imaging modality that has high sensitivity and negative predictive value for the detection of coronary artery disease (CAD). The main limitations of CCTA are its poor specificity and positive predictive value, as well as its inherent lack of physiologically relevant data on hemodynamic significance of coronary stenosis, a data that is provided either by non-invasive stress tests such as myocardial perfusion imaging (MPI) or invasively by measurement of the Fractional Flow Reserve (FFR). Recent advances in computational fluid dynamic techniques applied to standard CCTA are now emerging as powerful tools for virtual measurement of FFR from CCTA imaging (CT-FFR). These techniques correlate well with invasively measured FFR [1-4]. The primary purpose of this study is to evaluate the incremental benefit CT-FFR as compared to CCTA in triaging chest pain patients in emergency settings who are found to have obstructive CAD upon CCTA (generally >= 30% stenosis). Invasive FFR and short term clinical outcomes (90 days) will be correlated with each diagnostic modality in order to evaluate positive and negative predictive value of each.
Patients will undergo a CCTA, as part of routine emergency care. If the patient consents to participate in the study, the CCTA study will be assessed by Toshiba Software, to provide a computerized FFR reading, based on the CCTA study. If the noninvasive FFR diagnosis indicates obstructive disease, the patient will undergo cardiac catheterization with invasive FFR.
As CCTA utilization increases, the need to train additional imaging specialists will increase. This study will assess the capability of FFR-CT to enhance performance on both negative and positive predictive value for less experienced readers by providing feedback based on CT-FFR evaluation. If the use of CT-FFR improves accuracy of CCTA, as compared to the gold standard, (Invasive FFR), use of CT-FFR can potentially enhance performance for less experienced readers.
Detailed description
Background:
Coronary Computed Tomography Angiogram (CCTA) is a non-invasive imaging modality that has high sensitivity and negative predictive value for the detection of coronary artery disease (CAD). The main limitations of CCTA are its poor specificity and positive predictive value, as well as its inherent lack of physiologically relevant data on hemodynamic significance of coronary stenosis, a data that is provided either by non-invasive stress tests such as myocardial perfusion imaging (MPI) or invasively by measurement of the Fractional Flow Reserve (FFR). Recent advances in computational fluid dynamic techniques applied to standard CCTA are now emerging as powerful tools for virtual measurement of FFR from CCTA imaging (CT-FFR). These techniques correlate well with invasively measured FFR [1-4]. The primary purpose of this study is to evaluate the incremental benefit CT-FFR as compared to CCTA in triaging chest pain patients in ED settings who are found to have obstructive CAD upon CCTA (generally > 30% and < 90% stenosis). Invasive FFR and short term clinical outcomes (90 days) will be correlated with each diagnostic modality in order to evaluate positive and negative predictive value of each when used incrementally with CCTA.
Investigational Agent:
CCTA is increasingly becoming a preferred non-invasive imaging modality because of its high sensitivity and negative predictive value for the detection of CAD. It has been shown to be a robust imaging modality for evaluation of chest pain, and is associated with decreased unnecessary hospital admission, length of stay, major adverse cardiovascular event rates, recidivism rates, and downstream resource utilization compared to standard evaluation [5]. While findings so far are highly suggestive of CCTA's significance as a gatekeeper for ICA by ruling out obstructive CAD, fewer than half of obstructive stenosis identified by CCTA are ischemia-causing, signifying its poor positive predictive value and inherent lack of physiological information [6-8]. Consequently, utilization of CCTA has not entirely averted need for downstream testing for functional assessment of CCTA-detected obstructive lesions either by stress testing or ICA. Recently a major treatment modality, associated with the use of CCTA, has become available that offers promise for improving positive predictive value and physiological relevant hemodynamic data. Advances in computational fluid dynamic techniques applied to standard CCTA are now emerging as a powerful tool for virtual measurement of FFR from CCTA imaging (CT-FFR). This technique correlates well with invasively measured FFR [1-4]. While HeartFlow, Inc. has established an FDA approved process to assess coronary artery flow using noninvasive CT-FFR, this data requires 24 to 48 hours for processing.
Toshiba CT-FFR processing is non-FDA approved. The analytic method for vessel evaluation differs from that used by HeartFlow. Currently Toshiba is operating studies at four organizations around the world to assess the product's performance. Recently, the company published results from a study conducted Australia that showed positive findings on a sample of 42 patients, with positive predictive value of 74% vs. 60%.[9] The technology was presented at European Society of Cardiology (ESC) by Dr. S. Seneviratne and at Radiological Society of North America (RSNA) and the American Heart Association (AHA). Using the technology for ED patients offers potential advantage over the HeartFlow process, because the turnaround time for the procedure is one to three hours. However, the early positive findings need to be validated with a more robust study.
Preclinical Data:
While few publications regarding the use of CT-FFR specifically address the cost of diagnostic work-up for obstructive disease, it is clear that the cost structure resulting from changes in diagnostic testing will also change. Deferral or avoidance of cardiac catheterization and nuclear stress testing will likely yield significant reductions in the cost of the diagnostic testing. In addition, because the results of the CT-FFR are available in the ED, CT-FFR has the potential to offer financial savings from reduced length of stay, while increasing patient satisfaction and reducing exposure to increased risk related to the emergency department environment.
Clinical Data to Date:
From 1/1/2009 to 3/31/2015 the investigative team introduced and operated a CCTA Chest Pain triage program for low to intermediate risk patients at Stony Brook University Hospital ED and non-emergency outpatient services, the only tertiary care hospital in Suffolk County, New York (NY). Concurrently, the investigators established a registry to monitor patient outcomes for all patients receiving CCTA at Stony Brook Medicine. The registry contained nearly 15,000 patient CCTA procedures. The major registry study established the effectiveness of CCTA as an imaging modality for evaluating ED chest pain in a cost efficient manner with a false negative rate less than 1% [5]. However, the registry reflects the poorer positive predictive values documented by other industry studies [6-8].
False positive workup results in the necessity of performing cardiac catheterization on patients at risk for obstructive disease based on assessment with current standard of care (combined screening with CCTA and stress MPI). Reduction in the rate of false positive testing would lead to reduction in risk from invasive procedures and radiation exposure to patients and reduced cost to the health care system.
Study Objectives:
The purpose of this study is to evaluate the incremental benefit of Fractional Flow Reserve derived from CCTA (FFR-CT) compared to invasive FFR as the gold standard for patients with obstructive disease (generally, >= 30% stenosis).
General Study Design:
This will be a prospective clinical trial designed to evaluate the incremental benefit of virtual FFR measured from CCTA, compared to invasive FFR and CCTA alone for the detection of flow-limiting coronary stenosis, as defined by invasive FFR <=0.8 and vessel diameter of >=2mm.
1,142 consecutive patients who present to North Shore University Hospital Emergency Department (ED) for CCTA due to chest pain or angina over a two year period and meeting the study inclusion criteria are eligible for the study (Figure 1). The investigators will employ CCTA-appropriateness criteria to ensure proper selection of patients, derived from the Appropriate Use Criteria for Cardiac Computed Tomography published in 2010 and jointly authored by multiple societies including American College of Cardiology Foundation (ACCF), Society of Cardiovascular Computed Tomography (SCCT), and American College of Radiology (ACR) [11]. FFR-CT measurements will be performed following CCTA scan acquisition on software developed by Toshiba America Medical Systems, Inc. All eligible patients will undergo 320-slice multi detector CCTA and CT-FFR measurements. The severity of the stenosis will be determined on site by level III CCTA readers.
Patients with borderline (50% - 70%) or positive CCTA (>70%) stenosis readings will undergo ICA with invasive FFR measurement in accordance with accepted guidelines and established practice standard. Those patients with invasively measured FFR<=0.8 and with vessel diameter of >= 2mm, or those who require revascularizations based on invasively estimated stenosis severity (for patients who are totally obstructed) will be considered to have flow-limiting obstructive CAD, while the rest will be considered to have non-flow limiting obstructive CAD (if also >50% stenosis on ICA). If stenosis severity turns out to be < 50% after ICA, these patients will have been shown to have non-obstructive CAD. (Figure 1). Patients with 30% to 49% obstructive stenosis by CCTA standards and with positive CT-FFR, will also undergo invasive FFR and follow the protocol for those with > 50% obstruction. Patients with 0 to 49% obstructive disease and negative CT-FFR will be referred to optimal follow up care only.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: 1: Toshiba CT-FFR Arm | – | Device: Toshiba CT-FFRAll patients who consent will receive Toshiba CT-FFR and medically acceptable care based on the study protocol, commonly accepted standards of care, and the patients condition. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Low to intermediate risk chest pain patients (as defined by the criteria above presenting to North Shore University Hospital, Northwell Health, Manhasset, NY for emergent assessement of chest pain symptoms.
Key inclusion criteria (6 listed)
- Capable of giving informed consent.
- Able to cooperate with the technician performing the procedure.
- Patient must have Body Mass Index (BMI) <= 50.
- Patients must have non-ST Elevation Myocardial Infarction (STEMI) Electrocardiogram (EKG) without acute changes.
- Patients must present to North Shore University Hospital ED with Acute Chest Pain and require evaluation of coronary stenosis for the provisional diagnoses of acute chest pain or unstable angina or angina equivalent, and meet the criteria for CCTA by Heart Score Triage for the purpose of evaluation coronary stenosis for the provisional diagnoses of chest pain or angina or angina equivalent.
Key exclusion criteria (5 listed)
- Patients must not have a history of coronary stenting or coronary artery bypass graft.
- Patients must not have severe or end stage renal disease as diagnosed as estimated glomerular filtration rate (eGFR)<50.
- Patients must not have a BMI>50.
- Patient must not have any allergies to contrast.
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Toshiba CT-FFRAlso: Noninvasive CT-FFR, FFR-CT, Noninvasive FFR-CTPatients receiving CCTA to diagnose acute chest pain or unstable angina will receive CT-FFR to estimate rate of blood flow through the coronary arteries. The rate of flow will be compared to the rate found on Invasive FFR (the gold standard) if the subject receives invasive FFR. | Device | Experimental: 1: Toshiba CT-FFR Arm |
Primary outcome
Comparison of CT-FFR to Invasive FFR
Time frame: Up to 2 years from the study initiation will be required to enroll all study patients and obtain invasive and noninvasive FFR.
To evaluate sensitivity, specificity, positive and negative predictive value for CT-FFR, compared to invasive FFR.
2 secondary outcomes
Return Visits
Time frame: Up to 27 months will be required to collect 90 day follow up information on all study participants.
Economic Impact
Time frame: Up to 27 months will be requires to collect medical utilization after having administered CT-FFR
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2023.
- Background: PubMed 22922562Min JK, Leipsic J, Pencina MJ, Berman DS, Koo BK, van Mieghem C, Erglis A, Lin FY, Dunning AM, Apruzzese P, Budoff MJ, Cole JH, Jaffer FA, Leon MB, Malpeso J, Mancini GB, Park SJ, Schwartz RS, Shaw LJ, Mauri L. Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. JAMA. 2012 Sep 26;308(12):1237-45. doi: 10.1001/2012.jama.11274.
- Background: PubMed 24486266Norgaard BL, Leipsic J, Gaur S, Seneviratne S, Ko BS, Ito H, Jensen JM, Mauri L, De Bruyne B, Bezerra H, Osawa K, Marwan M, Naber C, Erglis A, Park SJ, Christiansen EH, Kaltoft A, Lassen JF, Botker HE, Achenbach S; NXT Trial Study Group. Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). J Am Coll Cardiol. 2014 Apr 1;63(12):1145-1155. doi: 10.1016/j.jacc.2013.11.043. Epub 2014 Jan 30.
- Background: PubMed 21810860Ko BS, Cameron JD, Meredith IT, Leung M, Antonis PR, Nasis A, Crossett M, Hope SA, Lehman SJ, Troupis J, DeFrance T, Seneviratne SK. Computed tomography stress myocardial perfusion imaging in patients considered for revascularization: a comparison with fractional flow reserve. Eur Heart J. 2012 Jan;33(1):67-77. doi: 10.1093/eurheartj/ehr268. Epub 2011 Aug 2.
- Background: PubMed 20726217Niska R, Bhuiya F, Xu J. National Hospital Ambulatory Medical Care Survey: 2007 emergency department summary. Natl Health Stat Report. 2010 Aug 6;(26):1-31.
- Background: PubMed 23684682Poon M, Cortegiano M, Abramowicz AJ, Hines M, Singer AJ, Henry MC, Viccellio P, Hellinger JC, Ferraro S, Poon A, Raff GL, Voros S, Farkouh ME, Noack P. Associations between routine coronary computed tomographic angiography and reduced unnecessary hospital admissions, length of stay, recidivism rates, and invasive coronary angiography in the emergency department triage of chest pain. J Am Coll Cardiol. 2013 Aug 6;62(6):543-52. doi: 10.1016/j.jacc.2013.04.040. Epub 2013 May 15.
- Background: PubMed 19007693Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, Scherer M, Bellinger R, Martin A, Benton R, Delago A, Min JK. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008 Nov 18;52(21):1724-32. doi: 10.1016/j.jacc.2008.07.031.
- Background: PubMed 19095130Meijboom WB, Meijs MF, Schuijf JD, Cramer MJ, Mollet NR, van Mieghem CA, Nieman K, van Werkhoven JM, Pundziute G, Weustink AC, de Vos AM, Pugliese F, Rensing B, Jukema JW, Bax JJ, Prokop M, Doevendans PA, Hunink MG, Krestin GP, de Feyter PJ. Diagnostic accuracy of 64-slice computed tomography coronary angiography: a prospective, multicenter, multivendor study. J Am Coll Cardiol. 2008 Dec 16;52(25):2135-44. doi: 10.1016/j.jacc.2008.08.058.
- Background: PubMed 27771399Ko BS, Cameron JD, Munnur RK, Wong DTL, Fujisawa Y, Sakaguchi T, Hirohata K, Hislop-Jambrich J, Fujimoto S, Takamura K, Crossett M, Leung M, Kuganesan A, Malaiapan Y, Nasis A, Troupis J, Meredith IT, Seneviratne SK. Noninvasive CT-Derived FFR Based on Structural and Fluid Analysis: A Comparison With Invasive FFR for Detection of Functionally Significant Stenosis. JACC Cardiovasc Imaging. 2017 Jun;10(6):663-673. doi: 10.1016/j.jcmg.2016.07.005. Epub 2016 Oct 19.
- Background: PubMed 19038879Miller JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, Paul N, Clouse ME, Shapiro EP, Hoe J, Lardo AC, Bush DE, de Roos A, Cox C, Brinker J, Lima JA. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med. 2008 Nov 27;359(22):2324-36. doi: 10.1056/NEJMoa0806576.
- Background: PubMed 21087721Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P, Rubin GD; American College of Cardiology Foundation Appropriate Use Criteria Task Force; Society of Cardiovascular Computed Tomography; American College of Radiology; American Heart Association; American Society of Echocardiography; American Society of Nuclear Cardiology; North American Society for Cardiovascular Imaging; Society for Cardiovascular Angiography and Interventions; Society for Cardiovascular Magnetic Resonance; Kramer CM, Berman D, Brown A, Chaudhry FA, Cury RC, Desai MY, Einstein AJ, Gomes AS, Harrington R, Hoffmann U, Khare R, Lesser J, McGann C, Rosenberg A, Schwartz R, Shelton M, Smetana GW, Smith SC Jr. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. J Am Coll Cardiol. 2010 Nov 23;56(22):1864-94. doi: 10.1016/j.jacc.2010.07.005.
- Results publication: PubMed 22032711Koo BK, Erglis A, Doh JH, Daniels DV, Jegere S, Kim HS, Dunning A, DeFrance T, Lansky A, Leipsic J, Min JK. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study. J Am Coll Cardiol. 2011 Nov 1;58(19):1989-97. doi: 10.1016/j.jacc.2011.06.066.
- Individual participant dataSharing planned: No. No Individual Participant Data (IPD) will be shared with other researchers. All study data will be deidentified to protect individual study participants identity.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Poon, MD principal investigator
Northwell Health
Shahryar Saba, MD study director
Northwell Health
Amar Shah, MD study director
Northwell Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Coronary Artery Disease and Chest Pain, run by Northwell Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of CT-FFR to Invasive FFR (time frame: Up to 2 years from the study initiation will be required to enroll all study patients and obtain invasive and noninvasive FFR.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03329469, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2023.