Role of On-site CT-derived FFR in the Management of Suspect CAD Patients

Coronary Artery Disease Clinical Trial

— TARGET  

Official title:

The Effect of On-site CT-derived Fractional Flow Reserve on the Management Making for the Patients With Stable Chest Pain (TARGET Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03901326
• Other study ID #: S2019-025-01
• Status: Recruiting
• Phase: N/A
• Start date: May 10, 2019
• Est. completion date: December 2021

Study information

• Verified date: August 2019
• Source: Chinese PLA General Hospital
• Contact: Junjie Yang, MD
• Phone: 86-13581662680
• Email: Fearlessyang[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Description:

Based on the clinical fact that less stress single photon emission computed tomography (SPECT) and stress magnetic resonance imaging (MRI) 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 registry is aim 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1216
• Est. completion date: December 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• New or worsening chest pain suspicious for clinically significant coronary artery disease

• Coronary CTA result showed that the diameter stenosis is more than 30% in one major coronary artery at least (coronary artery diameter greater than 2.5mm)

• Intermediate likelihood 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 urgent or emergent testing

• Hemodynamically or clinically unstable condition systolic blood pressure < 90 mmHg or serious atrial or ventricular arrhythmias

• Persistent resting chest pain felt to be ischemic despite adequate therapy

• 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

• Any invasive or non-invasive anatomic or functional cardiovascular test for detection of CAD, including ICA and exercise ECG within the previous 12 months

• Known significant congenital, valvular (moderate and above) or cardiomyopathy process (hypertrophic cardiomyopathy or reduced systolic left ventricular function = 40%) which could explain cardiac symptoms

• Contraindication to undergo coronary CTA, including but not limited to allergy to iodinated contrast agent, unable to receive ß-blockers if needed during CT procedural, pregnancy, serum creatinine =1.5 mg/dL

• Unable to provide written informed consent or participate in long-term follow-up

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Diagnostic Test:
• CT-FFR
When subjects are randomized to the CTA/CT-FFR arm, FFR based on the coronary CTA imaging will be measured. 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 2-3cm downstream of an interest lesion.

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing	Beijing

Sponsors (6)

Lead Sponsor	Collaborator
Chinese PLA General Hospital	Anzhen Hospital, Capital Medical University, Beijing, First Affiliated Hospital of Xinjiang Medical University, Qilu Hospital of Shandong University, Second Affiliated Hospital, School of Medicine, Zhejiang University, Tongji Hospital

Country where clinical trial is conducted

China, 

References & Publications (10)

Colleran R, Douglas PS, Hadamitzky M, Gutberlet M, Lehmkuhl L, Foldyna B, Woinke M, Hink U, Nadjiri J, Wilk A, Wang F, Pontone G, Hlatky MA, Rogers C, Byrne RA. An FFR(CT) diagnostic strategy versus usual care in patients with suspected coronary artery disease planned for invasive coronary angiography at German sites: one-year results of a subgroup analysis of the PLATFORM (Prospective Longitudinal Trial of FFR(CT): Outcome and Resource Impacts) study. Open Heart. 2017 Mar 22;4(1):e000526. doi: 10.1136/openhrt-2016-000526. eCollection 2017. — View Citation

Collet C, Onuma Y, Andreini D, Sonck J, Pompilio G, Mushtaq S, La Meir M, Miyazaki Y, de Mey J, Gaemperli O, Ouda A, Maureira JP, Mandry D, Camenzind E, Macron L, Doenst T, Teichgräber U, Sigusch H, Asano T, Katagiri Y, Morel MA, Lindeboom W, Pontone G, Lüscher TF, Bartorelli AL, Serruys PW. Coronary computed tomography angiography for heart team decision-making in multivessel coronary artery disease. Eur Heart J. 2018 Nov 1;39(41):3689-3698. doi: 10.1093/eurheartj/ehy581. — View Citation

Douglas PS, De Bruyne B, Pontone G, Patel MR, Norgaard BL, Byrne RA, Curzen N, Purcell I, Gutberlet M, Rioufol G, Hink U, Schuchlenz HW, Feuchtner G, Gilard M, Andreini D, Jensen JM, Hadamitzky M, Chiswell K, Cyr D, Wilk A, Wang F, Rogers C, Hlatky MA; PLATFORM Investigators. 1-Year Outcomes of FFRCT-Guided Care in Patients With Suspected Coronary Disease: The PLATFORM Study. J Am Coll Cardiol. 2016 Aug 2;68(5):435-445. doi: 10.1016/j.jacc.2016.05.057. — View Citation

Fairbairn TA, Nieman K, Akasaka T, Nørgaard BL, Berman DS, Raff G, Hurwitz-Koweek LM, Pontone G, Kawasaki T, Sand NP, Jensen JM, Amano T, Poon M, Øvrehus K, Sonck J, Rabbat M, Mullen S, De Bruyne B, Rogers C, Matsuo H, Bax JJ, Leipsic J, Patel MR. Real-world clinical utility and impact on clinical decision-making of coronary computed tomography angiography-derived fractional flow reserve: lessons from the ADVANCE Registry. Eur Heart J. 2018 Nov 1;39(41):3701-3711. doi: 10.1093/eurheartj/ehy530. — View Citation

Jensen JM, Bøtker HE, Mathiassen ON, Grove EL, Øvrehus KA, Pedersen KB, Terkelsen CJ, Christiansen EH, Maeng M, Leipsic J, Kaltoft A, Jakobsen L, Sørensen JT, Thim T, Kristensen SD, Krusell LR, Nørgaard BL. Computed tomography derived fractional flow reserve testing in stable patients with typical angina pectoris: influence on downstream rate of invasive coronary angiography. Eur Heart J Cardiovasc Imaging. 2018 Apr 1;19(4):405-414. doi: 10.1093/ehjci/jex068. — View Citation

Koo 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. — View Citation

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. — View Citation

Nørgaard BL, Hjort J, Gaur S, Hansson N, Bøtker HE, Leipsic J, Mathiassen ON, Grove EL, Pedersen K, Christiansen EH, Kaltoft A, Gormsen LC, Mæng M, Terkelsen CJ, Kristensen SD, Krusell LR, Jensen JM. Clinical Use of Coronary CTA-Derived FFR for Decision-Making in Stable CAD. JACC Cardiovasc Imaging. 2017 May;10(5):541-550. doi: 10.1016/j.jcmg.2015.11.025. Epub 2016 Apr 13. — View Citation

Nørgaard 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, Bøtker 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. — View Citation

Nørgaard BL, Terkelsen CJ, Mathiassen ON, Grove EL, Bøtker HE, Parner E, Leipsic J, Steffensen FH, Riis AH, Pedersen K, Christiansen EH, Mæng M, Krusell LR, Kristensen SD, Eftekhari A, Jakobsen L, Jensen JM. Coronary CT Angiographic and Flow Reserve-Guided Management of Patients With Stable Ischemic Heart Disease. J Am Coll Cardiol. 2018 Oct 30;72(18):2123-2134. doi: 10.1016/j.jacc.2018.07.043. Epub 2018 Aug 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of ICA without obstructive CAD or intervention	Percentage of those with planned ICA in whom no significant obstructive CAD (no stenosis=50% 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.	90 days
Secondary	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	90 days,6 months,12 months
Secondary	Medical expenditure	Medical expenditure by intention to treat at both 90 days and 12 months cumulatively	90 days,12 months
Secondary	Quality of life score	Quality of life score evaluated as quality of life (QOL), which is measured by Seattle Angina Questionnaire Scale, used 11-item instrument that measures patient reported symptoms, function and QOL for subjects with CAD within 12 months	12 months
Secondary	Cumulative radiation exposure	Cumulative radiation exposure for any examination within 90 days and 12 months	90 days, 12 months