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Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation (DEFINE-FLAIR)

Primary Purpose

Coronary Artery Disease

Status
Unknown status
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
iFR
FFR
Sponsored by
Imperial College London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Coronary Artery Disease

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Arnold Seto
  • John Altman
  • Habib Samady
  • Washington University School of Medicine
  • Allen Jeremias
  • Manesh Patel
  • Sam Lehman
  • Darren Walters
  • James Sapontis
  • Ravinay Bhindi
  • Christian Vrints
  • Luc Janssens
  • Ahmed Khashaba
  • Mika Laine
  • Florian Krackhardt
  • Olaf Going
  • Waldemar Bojara
  • Tobias Haerle
  • Ciro Indolfi
  • Giampaolo Nicolli
  • Flavio Ribichini
  • Hiroaki Takashima
  • Hiroyoshi Yokoi
  • Yuetsu Kikuta
  • Hitosh Matsuo
  • Nob Tanaka
  • Chang-Wook Nam
  • Joon-Hyung Doh
  • Bon-Kwon Koo
  • Eun-Seok Shin
  • Andrejs Erglis
  • Jan Piek
  • Niels Van Royen
  • Martijn Meuwissen
  • Hugo Vinhas
  • Sergio Baptista
  • Pedro Canas Silva
  • Ali Alghamadi
  • Farrel Hellig
  • Salvatore Brugaletta
  • Clinico San Carlos
  • Eduardo Alegria
  • Murat Sezer
  • Kare Tang
  • Suneel Talwar
  • Andrew Sharp
  • Imperial College London
  • Ranil De Silva
  • Rajesh Kharbanda
  • Robert Gerber

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

iFR

FFR

Arm Description

Treatment guided by iFR

Treatment guided by FFR

Outcomes

Primary Outcome Measures

Major Adverse Cardiac Events
Composite of death, myocardial infarction, unplanned revascularisation

Secondary Outcome Measures

Death (all cause)
Death (cardiovascular)
Myocardial Infarction
Repeat revascularisation
Cost associated to iFR or FFR measurement
Cost associated to iFR or FFR
Quality of life assessed by EQ-5D-5L and Seattle Angina Questionnaire
Cost savings of removing secondary investigations
7) Cost savings of removing secondary investigations, by assessing/treating non-culprit acute coronary syndrome (ACS) at the time of index presentation.

Full Information

First Posted
November 26, 2013
Last Updated
August 12, 2019
Sponsor
Imperial College London
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1. Study Identification

Unique Protocol Identification Number
NCT02053038
Brief Title
Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation
Acronym
DEFINE-FLAIR
Official Title
Prospective, Multi-center, Double Blind, Randomised Study to Test the Safety of Deferral of Stenting in Physiological Non-significant Lesions in a Clinical Population of Intermediate Stenoses Using iFR and FFR
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 2014 (Actual)
Primary Completion Date
January 19, 2021 (Anticipated)
Study Completion Date
January 19, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London

4. Oversight

Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
2500 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
iFR
Arm Type
Experimental
Arm Description
Treatment guided by iFR
Arm Title
FFR
Arm Type
Active Comparator
Arm Description
Treatment guided by FFR
Intervention Type
Device
Intervention Name(s)
iFR
Intervention Description
Treatment guided by instantaneous wave-free ratio
Intervention Type
Device
Intervention Name(s)
FFR
Intervention Description
Treatment guided by Fractional Flow Reserve
Primary Outcome Measure Information:
Title
Major Adverse Cardiac Events
Description
Composite of death, myocardial infarction, unplanned revascularisation
Time Frame
30 days, 1, 2 and 5 years
Secondary Outcome Measure Information:
Title
Death (all cause)
Time Frame
30 days, 1, 2 and 5 years
Title
Death (cardiovascular)
Time Frame
30 days, 1, 2 and 5 years
Title
Myocardial Infarction
Time Frame
30 days, 1, 2 and 5 years
Title
Repeat revascularisation
Time Frame
30 days, 1, 2 and 5 years
Title
Cost associated to iFR or FFR measurement
Description
Cost associated to iFR or FFR
Time Frame
30 days, 1, 2 and 5 years
Title
Quality of life assessed by EQ-5D-5L and Seattle Angina Questionnaire
Time Frame
30 days, 1, 2 and 5 years
Title
Cost savings of removing secondary investigations
Description
7) Cost savings of removing secondary investigations, by assessing/treating non-culprit acute coronary syndrome (ACS) at the time of index presentation.
Time Frame
30 days, 1, 2 and 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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) Exclusion criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Justin ER Davies, MD
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Javier Escaned, MD
Organizational Affiliation
Clinico San Carlos
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Patrick Serruys, MD
Organizational Affiliation
Imperial College London
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Manesh Patel, MD
Organizational Affiliation
Duke University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Sayan Sen, MD
Organizational Affiliation
Imperial College London
Official's Role
Study Director
Facility Information:
Facility Name
Arnold Seto
City
Long Beach
State/Province
California
Country
United States
Facility Name
John Altman
City
Lakewood
State/Province
Colorado
Country
United States
Facility Name
Habib Samady
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Allen Jeremias
City
Stony Brook
State/Province
New York
Country
United States
Facility Name
Manesh Patel
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
Sam Lehman
City
Adelaide
Country
Australia
Facility Name
Darren Walters
City
Brisbane
Country
Australia
Facility Name
James Sapontis
City
Melbourne
Country
Australia
Facility Name
Ravinay Bhindi
City
Sydney
Country
Australia
Facility Name
Christian Vrints
City
Antwerp
Country
Belgium
Facility Name
Luc Janssens
City
Bonheiden
Country
Belgium
Facility Name
Ahmed Khashaba
City
Cairo
Country
Egypt
Facility Name
Mika Laine
City
Helsinki
Country
Finland
Facility Name
Florian Krackhardt
City
Berlin
Country
Germany
Facility Name
Olaf Going
City
Berlin
Country
Germany
Facility Name
Waldemar Bojara
City
Koblenz
Country
Germany
Facility Name
Tobias Haerle
City
Oldenburg
Country
Germany
Facility Name
Ciro Indolfi
City
Catanzaro
Country
Italy
Facility Name
Giampaolo Nicolli
City
Rome
Country
Italy
Facility Name
Flavio Ribichini
City
Verona
Country
Italy
Facility Name
Hiroaki Takashima
City
Aichi
Country
Japan
Facility Name
Hiroyoshi Yokoi
City
Fukuoka
Country
Japan
Facility Name
Yuetsu Kikuta
City
Fukuyama
Country
Japan
Facility Name
Hitosh Matsuo
City
Gifu
Country
Japan
Facility Name
Nob Tanaka
City
Tokyo
Country
Japan
Facility Name
Chang-Wook Nam
City
Daegu
Country
Korea, Republic of
Facility Name
Joon-Hyung Doh
City
Daehwa
Country
Korea, Republic of
Facility Name
Bon-Kwon Koo
City
Seoul
Country
Korea, Republic of
Facility Name
Eun-Seok Shin
City
Ulsan
Country
Korea, Republic of
Facility Name
Andrejs Erglis
City
Riga
Country
Latvia
Facility Name
Jan Piek
City
Amsterdam
Country
Netherlands
Facility Name
Niels Van Royen
City
Amsterdam
Country
Netherlands
Facility Name
Martijn Meuwissen
City
Breda
Country
Netherlands
Facility Name
Hugo Vinhas
City
Almada
Country
Portugal
Facility Name
Sergio Baptista
City
Amadora
Country
Portugal
Facility Name
Pedro Canas Silva
City
Lisbon
Country
Portugal
Facility Name
Ali Alghamadi
City
Riyadh
Country
Saudi Arabia
Facility Name
Farrel Hellig
City
Johannesburg
Country
South Africa
Facility Name
Salvatore Brugaletta
City
Barcelona
Country
Spain
Facility Name
Clinico San Carlos
City
Madrid
Country
Spain
Facility Name
Eduardo Alegria
City
Madrid
Country
Spain
Facility Name
Murat Sezer
City
Istanbul
Country
Turkey
Facility Name
Kare Tang
City
Basildon
Country
United Kingdom
Facility Name
Suneel Talwar
City
Bournemouth
Country
United Kingdom
Facility Name
Andrew Sharp
City
Exeter
Country
United Kingdom
Facility Name
Imperial College London
City
London
Country
United Kingdom
Facility Name
Ranil De Silva
City
London
Country
United Kingdom
Facility Name
Rajesh Kharbanda
City
Oxford
Country
United Kingdom
Facility Name
Robert Gerber
City
St Leonards
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
31648764
Citation
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.
Results Reference
derived
PubMed Identifier
31314045
Citation
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.
Results Reference
derived
PubMed Identifier
28317458
Citation
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.
Results Reference
derived

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Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation

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