The Flash FFR Ⅱ Study

Coronary Artery Disease Clinical Trial

Official title:

A Prospective, Multicenter, Blinded, Randomized, Noninferiority Clinical Trial of Coronary Angiography Fractional Flow Reserve (caFFR) Versus Fractional Flow Reserve (FFR) to Guide Percutaneous Coronary Intervention（Flash FFR Ⅱ ）

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04575207
• Other study ID #: SZRMD2020001
• Status: Recruiting
• Phase: N/A
• Start date: January 12, 2021
• Est. completion date: December 2025

Study information

• Verified date: March 2023
• Source: Peking University First Hospital
• Contact: Yanjun Gong, MD
• Phone: 8610-83575607
• Email: gongyanjun111[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall purpose of Flash FFR Ⅱ is to investigate whether coronary angiography-derived fractional flow reserve (caFFR), compared with fractional flow reserve (FFR) measured by a pressure wire, has non-inferior clinical effect and cost benefit in guiding the percutaneous coronary intervention (PCI) for patients with moderate coronary artery stenosis in terms of long-term clinical prognosis.

Description:

Flash FFR Ⅱ is a prospective, multicenter, blinded, randomized, non-inferiority trial. Eligible patients with moderate coronary artery stenosis will be included in the study and randomly assigned to either caFFR-guided group or FFR-guided group. Participant caFFR or FFR will be used to guide percutaneous coronary intervention (PCI) strategy.

The rate of major cardiovascular adverse events (MACE) and the cost data will be collected during the long-term follow-up (2 years). MACE is defined as a composite of all-cause death, myocardial infarction (MI), unplanned revascularization. Clinical outcomes and cost-effectiveness will be compared between the two groups.

A subgroup analysis is pre-set and included in the protocol, including age, sex, body mass index, diabetes mellitus, smoking status, mean aortic pressure (resting state), acute coronary syndrome, left ventricular ejection fraction, lesion site, lesion stenosis severity, target vessel reference diameter, small vessel lesion, blood flow velocity, PCI mode, and so on.

The trial is equipped with a core laboratory. Some interesting sub-studies will be carried out, such as a comparison of laboratory and operator analysis results.

If the trial results show non-inferiority, it should be noted that caFFR can bring new benefits to both operators and patients as a new index of physiological assessment of coronary artery stenosis severity with the advantages of lower cost, less risk, faster time, and less use of resources.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2132
• Est. completion date: December 2025
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• General inclusion criteria:

1. Age above 18 years old, no limit on the gender;

2. Angiography is considered necessary and feasible by investigator, and PCI will be performed if necessary;

3. Suspected coronary heart disease, stable angina pectoris, unstable angina pectoris, non-culprit vascular assessment in participants with acute non-ST-segment elevation myocardial infarction, and non-culprit vascular assessment in patients with previous ST-segment elevation acute myocardial infarction;

4. Participants voluntarily participate in this clinical trial and sign informed consent form.

• Coronary angiography inclusion criteria:

The presence of at least one stenosis and meets the following imaging findings:

1. The degree of coronary artery stenosis=50% and =90% by visual measurement;

2. The reference diameter of the stenotic segment=2.25 mm by visual measurement;

3. The investigator visually observes the target vessel through angiographic images, and consider that PCI surgery is technically feasible.

Exclusion Criteria:

• General exclusion criteria:

1. Acute ST-segment elevation myocardial infarction within 6 days;

2. Cardiogenic shock or left ventricular ejection fraction=50%;

3. eGFR < 30 mL/min (1.73 m2);

4. Severe coagulation dysfunctions or bleeding disorders;

5. Allergic to iodine contrast medium or contraindications for adenosine administration;

6. Severe aortic stenosis;

7. Life expectancy less than 1 year;

8. Pregnant women or women planning a recent pregnancy;

9. Participation in any other clinical trials of devices or drugs (ongoing or within the past 1 month);

10. The investigator believes that the particitant has other conditions that are not suitable for clinical trials.

• Coronary angiography exclusion criteria:

1. TIMI flow in the target vessel<grade III ;

2. Presence of myocardial bridge and systolic compression =50% in the target vessel;

3. Presence of artificial bypass in the target vessel;

4. Left main coronary artery or right coronary artery ostial lesions;

5. Stent implantation in the target vessel within 3 months;

6. Target vessel provides collateral support to chronically total occluded vessels;

7. Presence of factors affecting angiographic analysis and stenosis visualization, including incomplete vessel opacification, or overlap with other coronary branches of extreme vessel foreshortening.

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Angina Pectoris
• Angina, Stable
• Angina, Unstable
• Asymptomatic Ischemia
• Coronary Artery Disease
• Coronary Circulation
• Coronary Disease
• Coronary Stenosis
• Ischemia
• Myocardial Infarction
• Myocardial Ischaemia
• Myocardial Ischemia
• Percutaneous Coronary Intervention
• Stable Angina Pectoris
• Unstable Angina Pectoris

Intervention

Diagnostic Test:
• caFFR
caFFR is a new index of physiological assessment of coronary artery stenosis severity, based on angiographic images. Through two-dimensional analysis and three-dimensional reconstruction of two coronary angiography image series with an angle-off > 30 degrees, combined with fluid mechanics, TIMI frame counting method, and optimized CFD algorithm, the pressure drop from coronary ostium to every point in the vessel can be obtained, and then the caFFR value of each point in the vessel can be computed. The cutoff value in this trial is caFFR = 0.80 for myocardial ischemia.
• FFR
FFR is a widely used, pressure-based functional assessment index of coronary stenoses obtained with an intracoronary pressure wire fitted with pressure sensors. The pressure wire passes through the stenosis and directly measures the pressure distal to the stenosis. FFR value can be obtained by combining the pressure at the coronary ostium and the distal pressure to the stenosis. The cutoff value in this trial is FFR = 0.80 for myocardial ischemia.

Locations

Country	Name	City	State
China	Department of Cardiology, Peking University First Hospital	Beijing
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	The People's Hospital of Hebi	Hebi	Henan
China	QILU Hospital of Shandong University	Jinan	Shandong
China	Affiliated Hospital of Yunnan University	Kunming	Yunnan
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	Beijing Hospital of Traditional Chinese Medicine, Capital Medical University	Peking	Beijing
China	Peking University People's Hospital	Peking	Beijing
China	Zhongshan Hospital affiliated to Fudan University	Shanghai	Shanghai
China	The University of Hong Kong Shenzhen hospital	Shenzhen	Guangdong
China	Xiamen Cardiovascular Hospital Xiamen University	Xiamen	Fujian
China	The First Affiliated Hospital of Xinxiang Medical College	Xinxiang	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Peking University First Hospital	Rainmed Ltd., Suzhou, China

Country where clinical trial is conducted

China, 

References & Publications (5)

Davies JE, Sen S, Dehbi HM, Al-Lamee R, Petraco R, Nijjer SS, Bhindi R, Lehman SJ, Walters D, Sapontis J, Janssens L, Vrints CJ, Khashaba A, Laine M, Van Belle E, Krackhardt F, Bojara W, Going O, Harle T, Indolfi C, Niccoli G, Ribichini F, Tanaka N, Yokoi H, Takashima H, Kikuta Y, Erglis A, Vinhas H, Canas Silva P, Baptista SB, Alghamdi A, Hellig F, Koo BK, Nam CW, Shin ES, Doh JH, Brugaletta S, Alegria-Barrero E, Meuwissen M, Piek JJ, van Royen N, Sezer M, Di Mario C, Gerber RT, Malik IS, Sharp ASP, Talwar S, Tang K, Samady H, Altman J, Seto AH, Singh J, Jeremias A, Matsuo H, Kharbanda RK, Patel MR, Serruys P, Escaned J. Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI. N Engl J Med. 2017 May 11;376(19):1824-1834. doi: 10.1056/NEJMoa1700445. Epub 2017 Mar 18. — View Citation

De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PA, Piroth Z, Jagic N, Mobius-Winkler S, Rioufol G, Witt N, Kala P, MacCarthy P, Engstrom T, Oldroyd KG, Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Juni P, Fearon WF; FAME 2 Trial Investigators. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012 Sep 13;367(11):991-1001. doi: 10.1056/NEJMoa1205361. Epub 2012 Aug 27. Erratum In: N Engl J Med. 2012 Nov;367(18):1768. Mobius-Winckler, Sven [corrected to Mobius-Winkler, Sven]. — View Citation

Gotberg M, Christiansen EH, Gudmundsdottir IJ, Sandhall L, Danielewicz M, Jakobsen L, Olsson SE, Ohagen P, Olsson H, Omerovic E, Calais F, Lindroos P, Maeng M, Todt T, Venetsanos D, James SK, Karegren A, Nilsson M, Carlsson J, Hauer D, Jensen J, Karlsson AC, Panayi G, Erlinge D, Frobert O; iFR-SWEDEHEART Investigators. Instantaneous Wave-free Ratio versus Fractional Flow Reserve to Guide PCI. N Engl J Med. 2017 May 11;376(19):1813-1823. doi: 10.1056/NEJMoa1616540. Epub 2017 Mar 18. — View Citation

Li J, Gong Y, Wang W, Yang Q, Liu B, Lu Y, Xu Y, Huo Y, Yi T, Liu J, Li Y, Xu S, Zhao L, Ali ZA, Huo Y. Accuracy of computational pressure-fluid dynamics applied to coronary angiography to derive fractional flow reserve: FLASH FFR. Cardiovasc Res. 2020 Jun 1;116(7):1349-1356. doi: 10.1093/cvr/cvz289. — View Citation

Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van' t Veer M, Klauss V, Manoharan G, Engstrom T, Oldroyd KG, Ver Lee PN, MacCarthy PA, Fearon WF; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009 Jan 15;360(3):213-24. doi: 10.1056/NEJMoa0807611. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MACE	A composite of all-cause death, myocardial infarction (MI), and unplanned revascularization	1 year
Secondary	MACE(excluding PCI-related MI)	A composite of all-cause death, myocardial infarction (excluding PCI-related), and unplanned revascularization	1 month, 1 year, 2 years
Secondary	Death	Cardiovascular, non-cardiovascular, and undetermined death	1 month, 6 months, 1 year, 2 years
Secondary	MI	Target vessel related and non-target vessel related MI	1 month, 6 months, 1 year, 2 years
Secondary	Target vessel revascularization (TVR)	The ischemia driven and non-ischemia driven TVR	1 month, 6 months, 1 year, 2 years
Secondary	Any coronary artery revascularization	The ischemia driven and non-ischemia driven revascularization	1 month, 6 months, 1 year, 2 years
Secondary	Definite or probable stent thrombosis	Definite and probable stent thrombosis during acute, sub-acute, late, and very late phase	1 month, 6 months, 1 year, 2 years
Secondary	Evaluation of health economics	Cost-utility analysis and computation of incremental cost-effectiveness ratio.	1 month, 6 months, 1 year
Secondary	Analysis of participant discomfort during the operation (none/mild/moderate/severe )	During the caFFR or FFR detection, the operator will ask the participant if there is discomfort (none/mild/moderate/severe ) and what kind of discomfort(such as palpitation, chest stuffy , nausea, dizziness, foreign body invasion ), and fill out a questionnaire after the operation.The discomfort of all participants caused by the use of drugs, intervention, etc. during the caFFR or FFR detection will be analyzed.	During the operation
Secondary	The changes of PCI strategy depending on caFFR/FFR information	Before randomization,the operators will be asked to provide their planned treatment strategy based on the angiographic information alone.; After randomization and functional assessment,we will record how caFFR/FFR changed the treatment strategy.	During the operation