Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation

NCT02053038 | Unknown

• 1 other identifier: 13SM1797
• Study Type: interventional
• Target: 2,500
• Locations: 17 countries
• Sites: 50

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.

Conditions

Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• Major Adverse Cardiac Events

  Composite of death, myocardial infarction, unplanned revascularisation

  30 days, 1, 2 and 5 years

Secondary Outcomes (7)

• Death (all cause)

  30 days, 1, 2 and 5 years

• Death (cardiovascular)

  30 days, 1, 2 and 5 years

• Myocardial Infarction

  30 days, 1, 2 and 5 years

• Repeat revascularisation

  30 days, 1, 2 and 5 years

• Cost associated to iFR or FFR measurement

  30 days, 1, 2 and 5 years

Study Arms (2)

iFR

EXPERIMENTAL

Treatment guided by iFR

Device: iFR

FFR

ACTIVE COMPARATOR

Treatment guided by FFR

Device: FFR

Interventions

iFR DEVICE

Treatment guided by instantaneous wave-free ratio

iFR

FFR DEVICE

Treatment guided by Fractional Flow Reserve

FFR

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years of age
• Willing to participate and able to understand, read and sign the informed consent document before the planned procedure
• Eligible for coronary angiography and/or percutaneous coronary intervention
• 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).
• Stable angina or acute coronary syndrome (non-culprit vessels only and outside of primary intervention during acute STEMI)

You may not qualify if:

• Previous Coronary Artery Bypass surgery with patent grafts to the interrogated vessel
• Significant left main stenosis (\>50% narrowing)
• 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)
• 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
• Restenotic lesions
• Hemodynamic instability at the time of intervention (heart rate\<50 beats per minute, systolic blood pressure \<90mmHg), balloon pump
• Significant contraindication to adenosine administration (e.g. heart block, severe asthma)
• Contraindications to PCI (percutaneous coronary intervention) or drug-eluting stent (DES) implantation
• Heavily calcified or tortuous vessels
• 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
• Pregnancy
• STEMI (ST elevation myocardial infarction) within 48 hours of procedure
• Severe valvular heart disease
• ACS patients in whom more than one target vessel is present

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (50)

Arnold Seto

Long Beach, California, United States

Location

John Altman

Lakewood, Colorado, United States

Location

Habib Samady

Atlanta, Georgia, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Allen Jeremias

Stony Brook, New York, United States

Location

Manesh Patel

Durham, North Carolina, United States

Location

Sam Lehman

Adelaide, Australia

Location

Darren Walters

Brisbane, Australia

Location

James Sapontis

Melbourne, Australia

Location

Ravinay Bhindi

Sydney, Australia

Location

Christian Vrints

Antwerp, Belgium

Location

Luc Janssens

Bonheiden, Belgium

Location

Ahmed Khashaba

Cairo, Egypt

Location

Mika Laine

Helsinki, Finland

Location

Florian Krackhardt

Berlin, Germany

Location

Olaf Going

Berlin, Germany

Location

Waldemar Bojara

Koblenz, Germany

Location

Tobias Haerle

Oldenburg, Germany

Location

Ciro Indolfi

Catanzaro, Italy

Location

Giampaolo Nicolli

Rome, Italy

Location

Flavio Ribichini

Verona, Italy

Location

Hiroaki Takashima

Aichi, Japan

Location

Hiroyoshi Yokoi

Fukuoka, Japan

Location

Yuetsu Kikuta

Fukuyama, Japan

Location

Hitosh Matsuo

Gifu, Japan

Location

Nob Tanaka

Tokyo, Japan

Location

Andrejs Erglis

Riga, Latvia

Location

Jan Piek

Amsterdam, Netherlands

Location

Niels Van Royen

Amsterdam, Netherlands

Location

Martijn Meuwissen

Breda, Netherlands

Location

Hugo Vinhas

Almada, Portugal

Location

Sergio Baptista

Amadora, Portugal

Location

Pedro Canas Silva

Lisbon, Portugal

Location

Ali Alghamadi

Riyadh, Saudi Arabia

Location

Farrel Hellig

Johannesburg, South Africa

Location

Chang-Wook Nam

Daegu, South Korea

Location

Joon-Hyung Doh

Daehwa, South Korea

Location

Bon-Kwon Koo

Seoul, South Korea

Location

Eun-Seok Shin

Ulsan, South Korea

Location

Salvatore Brugaletta

Barcelona, Spain

Location

Clinico San Carlos

Madrid, Spain

Location

Eduardo Alegria

Madrid, Spain

Location

Murat Sezer

Istanbul, Turkey (Türkiye)

Location

Kare Tang

Basildon, United Kingdom

Location

Suneel Talwar

Bournemouth, United Kingdom

Location

Andrew Sharp

Exeter, United Kingdom

Location

Imperial College London

London, United Kingdom

Location

Ranil De Silva

London, United Kingdom

Location

Rajesh Kharbanda

Oxford, United Kingdom

Location

Robert Gerber

St Leonards, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 39412778 DERIVED

• 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.

  PMID: 37634144 DERIVED

• 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.

  PMID: 31648764 DERIVED

• 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.

  PMID: 31314045 DERIVED

• 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.

  PMID: 28317458 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Justin ER Davies, MD

  Imperial College London

  PRINCIPAL INVESTIGATOR

• Javier Escaned, MD

  Clinico San Carlos

  PRINCIPAL INVESTIGATOR

• Patrick Serruys, MD

  Imperial College London

  STUDY CHAIR

• Manesh Patel, MD

  Duke University

  STUDY CHAIR

• Sayan Sen, MD

  Imperial College London

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2013
• First Posted: February 3, 2014
• Study Start: January 1, 2014
• Primary Completion: January 19, 2021
• Study Completion: January 19, 2021
• Last Updated: August 14, 2019

Record last verified: 2019-08

Locations

JP (5); EG (1); FI (1); TU (1); NL (3); IT (3); SA (1); DE (4); GB (7); PT (3); ZA (1); AU (4); KR (4); US (6); ES (3); BE (2); LA (1)