Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation

NCT ID: NCT02053038

Last Updated: 2019-08-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 2500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2021-01-19

Brief Summary

Narrowing of coronary arteries interferes with blood flow and can cause chest pain. But patients may have more than one narrowing and studies have shown that not all narrowings need to be treated. To identify the narrowings that need treating cardiologists sometimes quantify the extent of the narrowing by measuring fractional flow reserve (FFR, the ratio of the pressure in the aorta to the pressure downstream of the narrowing).This technique requires the administration of drugs that add cost and time to the procedure and in some countries are simply unavailable. As a result despite the clear health and healthcare costs benefits of FFR its use is limited to less than 5% of procedure. We have developed a new technique called the instantaneous wave-free ratio (iFR) that does not require the administration of drugs for its accurate assessment. It has been approved for use in this indication. This study aims to compare clinical outcomes of patients whose treatment has been guided by iFR to those whose treatment has been guided by FFR. If iFR is found to provide the same clinical outcomes as FFR its adoption will permit the clear benefits of this approach of identifying the coronary narrowings that really need treatment to be applicable to a much larger patient population and further improve healthcare costs.

Detailed Description

Design:

Patients with one or more coronary stenoses, in which the physiological severity from coronary angiography is in question, will be randomised 1:1 to use of the instantaneous wave free ratio (iFR) or fractional flow reserve (FFR) to guide the treatment strategy for percutaneous coronary intervention (PCI).

Aims:

To assess whether the iFR is non-inferior to FFR when used to guide treatment of coronary stenosis with PCI.

Outcome measures:

The primary endpoint will be major adverse cardiac event rate in the iFR and FFR groups at 30 days, 1, 2, and 5 years.

Population:

This will be an international multi-centre study of 2500 patients. From population estimates, 35% of the total study population will present with stable angina and 65% will have acute coronary syndrome.

Eligibility:

Patients will be eligible when the physiological severity of a stenosis within a vessel is in question. In the cases of stable angina this will be confined to the target vessel, or with acute coronary syndrome assessment this will be made in the non-culprit vessel.

Duration:

Anticipated recruitment is 12 months. Follow-up will be performed at 30 days, 1, 2 and 5 years.

Results:

Primary outcome results will be reported in Spring 2017.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: DOUBLE

Study Groups

iFR

Treatment guided by iFR

Group Type: EXPERIMENTAL

iFR

Intervention Type: DEVICE

Treatment guided by instantaneous wave-free ratio

FFR

Treatment guided by FFR

Group Type: ACTIVE_COMPARATOR

FFR

Intervention Type: DEVICE

Treatment guided by Fractional Flow Reserve

Interventions

iFR

Treatment guided by instantaneous wave-free ratio

Intervention Type: DEVICE

FFR

Treatment guided by Fractional Flow Reserve

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Age > 18 years of age

2. Willing to participate and able to understand, read and sign the informed consent document before the planned procedure

3. Eligible for coronary angiography and/or percutaneous coronary intervention

4. Coronary artery disease with at least 1 or more native major epicardial vessels or their branches by coronary angiogram with visually assessed de novo coronary stenosis in which the physiological severity of the lesion is in question (typically 40-70% diameter stenosis).

5. Stable angina or acute coronary syndrome (non-culprit vessels only and outside of primary intervention during acute STEMI)

Exclusion Criteria

1. Previous Coronary Artery Bypass surgery with patent grafts to the interrogated vessel

2. Significant left main stenosis (>50% narrowing)

3. Tandem stenoses separated by more than 10 mm that require separate pressure guide wire interrogation or percutaneous coronary intervention (PCI) (not to be interrogated or treated as a single stenosis)

4. Total coronary occlusions (CTOs). NOTE: Patients with CTOs can be included if i) treatment of the CTO is completed first, ii) the CTO PCI is successful, iii) the CTO PCI is successful and iii) the physiological lesion is in another vessel

5. Restenotic lesions

6. Hemodynamic instability at the time of intervention (heart rate<50 beats per minute, systolic blood pressure <90mmHg), balloon pump

7. Significant contraindication to adenosine administration (e.g. heart block, severe asthma)

8. Contraindications to PCI (percutaneous coronary intervention) or drug-eluting stent (DES) implantation

9. Heavily calcified or tortuous vessels

10. Significant hepatic or lung disease (chronic pulmonary obstructive disease), and/or malignant disease with unfavourable prognosis that may influence survival within the next 5 years

11. Pregnancy

12. STEMI (ST elevation myocardial infarction) within 48 hours of procedure

13. Severe valvular heart disease

14. ACS patients in whom more than one target vessel is present

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Justin ER Davies, MD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Javier Escaned, MD

Role: PRINCIPAL_INVESTIGATOR

Clinico San Carlos

Patrick Serruys, MD

Role: STUDY_CHAIR

Imperial College London

Manesh Patel, MD

Role: STUDY_CHAIR

Duke University

Sayan Sen, MD

Role: STUDY_DIRECTOR

Imperial College London

Locations

Arnold Seto

Long Beach, California, United States

John Altman

Lakewood, Colorado, United States

Habib Samady

Atlanta, Georgia, United States

Washington University School of Medicine

St Louis, Missouri, United States

Allen Jeremias

Stony Brook, New York, United States

Manesh Patel

Durham, North Carolina, United States

Sam Lehman

Adelaide, , Australia

Darren Walters

Brisbane, , Australia

James Sapontis

Melbourne, , Australia

Ravinay Bhindi

Sydney, , Australia

Christian Vrints

Antwerp, , Belgium

Luc Janssens

Bonheiden, , Belgium

Ahmed Khashaba

Cairo, , Egypt

Mika Laine

Helsinki, , Finland

Florian Krackhardt

Berlin, , Germany

Olaf Going

Berlin, , Germany

Waldemar Bojara

Koblenz, , Germany

Tobias Haerle

Oldenburg, , Germany

Ciro Indolfi

Catanzaro, , Italy

Giampaolo Nicolli

Rome, , Italy

Flavio Ribichini

Verona, , Italy

Hiroaki Takashima

Aichi, , Japan

Hiroyoshi Yokoi

Fukuoka, , Japan

Yuetsu Kikuta

Fukuyama, , Japan

Hitosh Matsuo

Gifu, , Japan

Nob Tanaka

Tokyo, , Japan

Andrejs Erglis

Riga, , Latvia

Jan Piek

Amsterdam, , Netherlands

Niels Van Royen

Amsterdam, , Netherlands

Martijn Meuwissen

Breda, , Netherlands

Hugo Vinhas

Almada, , Portugal

Sergio Baptista

Amadora, , Portugal

Pedro Canas Silva

Lisbon, , Portugal

Ali Alghamadi

Riyadh, , Saudi Arabia

Farrel Hellig

Johannesburg, , South Africa

Chang-Wook Nam

Daegu, , South Korea

Joon-Hyung Doh

Daehwa, , South Korea

Bon-Kwon Koo

Seoul, , South Korea

Eun-Seok Shin

Ulsan, , South Korea

Salvatore Brugaletta

Barcelona, , Spain

Clinico San Carlos

Madrid, , Spain

Eduardo Alegria

Madrid, , Spain

Murat Sezer

Istanbul, , Turkey (Türkiye)

Kare Tang

Basildon, , United Kingdom

Suneel Talwar

Bournemouth, , United Kingdom

Andrew Sharp

Exeter, , United Kingdom

Imperial College London

London, , United Kingdom

Ranil De Silva

London, , United Kingdom

Rajesh Kharbanda

Oxford, , United Kingdom

Robert Gerber

St Leonards, , United Kingdom

Countries

United States; Australia; Belgium; Egypt; Finland; Germany; Italy; Japan; Latvia; Netherlands; Portugal; Saudi Arabia; South Africa; South Korea; Spain; Turkey (Türkiye); United Kingdom

References

Escaned J, Travieso A, Dehbi HM, Nijjer SS, Sen S, Petraco R, Patel M, Serruys PW, Davies J; DEFINE FLAIR Investigators. Coronary Revascularization Guided With Fractional Flow Reserve or Instantaneous Wave-Free Ratio: A 5-Year Follow-Up of the DEFINE FLAIR Randomized Clinical Trial. JAMA Cardiol. 2025 Jan 1;10(1):25-31. doi: 10.1001/jamacardio.2024.3314.

Reference Type: DERIVED

PMID: 39412778 (View on PubMed)

Eftekhari A, Holck EN, Westra J, Olsen NT, Bruun NH, Jensen LO, Engstrom T, Christiansen EH. Instantaneous wave free ratio vs. fractional flow reserve and 5-year mortality: iFR SWEDEHEART and DEFINE FLAIR. Eur Heart J. 2023 Nov 1;44(41):4376-4384. doi: 10.1093/eurheartj/ehad582.

Reference Type: DERIVED

PMID: 37634144 (View on PubMed)

Kim CH, Koo BK, Dehbi HM, Lee JM, Doh JH, Nam CW, Shin ES, Cook CM, Al-Lamee R, Petraco R, Sen S, Malik IS, Nijjer SS, Mejia-Renteria H, Alegria-Barrero E, Alghamdi A, Altman J, Baptista SB, Bhindi R, Bojara W, Brugaletta S, Silva PC, Di Mario C, Erglis A, Gerber RT, Going O, Harle T, Hellig F, Indolfi C, Janssens L, Jeremias A, Kharbanda RK, Khashaba A, Kikuta Y, Krackhardt F, Laine M, Lehman SJ, Matsuo H, Meuwissen M, Niccoli G, Piek JJ, Ribichini F, Samady H, Sapontis J, Seto AH, Sezer M, Sharp ASP, Singh J, Takashima H, Talwar S, Tanaka N, Tang K, Van Belle E, van Royen N, Vinhas H, Vrints CJ, Walters D, Yokoi H, Samuels B, Buller C, Patel MR, Serruys PW, Escaned J, Davies JE. Sex Differences in Instantaneous Wave-Free Ratio or Fractional Flow Reserve-Guided Revascularization Strategy. JACC Cardiovasc Interv. 2019 Oct 28;12(20):2035-2046. doi: 10.1016/j.jcin.2019.06.035.

Reference Type: DERIVED

PMID: 31648764 (View on PubMed)

DEFINE-FLAIR Trial Investigators; Lee JM, Choi KH, Koo BK, Dehbi HM, Doh JH, Nam CW, Shin ES, Cook CM, Al-Lamee R, Petraco R, Sen S, Malik IS, Nijjer SS, Mejia-Renteria H, Alegria-Barrero E, Alghamdi A, Altman J, Baptista SB, Bhindi R, Bojara W, Brugaletta S, Silva PC, Di Mario C, Erglis A, Gerber RT, Going O, Harle T, Hellig F, Indolfi C, Janssens L, Jeremias A, Kharbanda RK, Khashaba A, Kikuta Y, Krackhardt F, Laine M, Lehman SJ, Matsuo H, Meuwissen M, Niccoli G, Piek JJ, Ribichini F, Samady H, Sapontis J, Seto AH, Sezer M, Sharp ASP, Singh J, Takashima H, Talwar S, Tanaka N, Tang K, Van Belle E, van Royen N, Vinhas H, Vrints CJ, Walters D, Yokoi H, Samuels B, Buller C, Patel MR, Serruys P, Escaned J, Davies JE. Comparison of Major Adverse Cardiac Events Between Instantaneous Wave-Free Ratio and Fractional Flow Reserve-Guided Strategy in Patients With or Without Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2019 Sep 1;4(9):857-864. doi: 10.1001/jamacardio.2019.2298.

Reference Type: DERIVED

PMID: 31314045 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28317458 (View on PubMed)

Other Identifiers

13SM1797

Identifier Type: -

Identifier Source: org_study_id