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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02053038




Registration number
NCT02053038
Ethics application status
Date submitted
26/11/2013
Date registered
3/02/2014
Date last updated
14/08/2019

Titles & IDs
Public title
Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation
Scientific 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
Secondary ID [1] 0 0
13SM1797
Universal Trial Number (UTN)
Trial acronym
DEFINE-FLAIR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary Artery Disease 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - iFR
Treatment: Devices - FFR

Experimental: iFR - Treatment guided by iFR

Active comparator: FFR - Treatment guided by FFR


Treatment: Devices: iFR
Treatment guided by instantaneous wave-free ratio

Treatment: Devices: FFR
Treatment guided by Fractional Flow Reserve
Intervention code [1] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Major Adverse Cardiac Events
Timepoint [1] 0 0
30 days, 1, 2 and 5 years
Secondary outcome [1] 0 0
Death (all cause)
Timepoint [1] 0 0
30 days, 1, 2 and 5 years
Secondary outcome [2] 0 0
Death (cardiovascular)
Timepoint [2] 0 0
30 days, 1, 2 and 5 years
Secondary outcome [3] 0 0
Myocardial Infarction
Timepoint [3] 0 0
30 days, 1, 2 and 5 years
Secondary outcome [4] 0 0
Repeat revascularisation
Timepoint [4] 0 0
30 days, 1, 2 and 5 years
Secondary outcome [5] 0 0
Cost associated to iFR or FFR measurement
Timepoint [5] 0 0
30 days, 1, 2 and 5 years
Secondary outcome [6] 0 0
Quality of life assessed by EQ-5D-5L and Seattle Angina Questionnaire
Timepoint [6] 0 0
30 days, 1, 2 and 5 years
Secondary outcome [7] 0 0
Cost savings of removing secondary investigations
Timepoint [7] 0 0
30 days, 1, 2 and 5 years

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
19/01/2021
Actual
Sample size
Target
2500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sam Lehman - Adelaide
Recruitment hospital [2] 0 0
Darren Walters - Brisbane
Recruitment hospital [3] 0 0
James Sapontis - Melbourne
Recruitment hospital [4] 0 0
Ravinay Bhindi - Sydney
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
Belgium
State/province [7] 0 0
Antwerp
Country [8] 0 0
Belgium
State/province [8] 0 0
Bonheiden
Country [9] 0 0
Egypt
State/province [9] 0 0
Cairo
Country [10] 0 0
Finland
State/province [10] 0 0
Helsinki
Country [11] 0 0
Germany
State/province [11] 0 0
Berlin
Country [12] 0 0
Germany
State/province [12] 0 0
Koblenz
Country [13] 0 0
Germany
State/province [13] 0 0
Oldenburg
Country [14] 0 0
Italy
State/province [14] 0 0
Catanzaro
Country [15] 0 0
Italy
State/province [15] 0 0
Rome
Country [16] 0 0
Italy
State/province [16] 0 0
Verona
Country [17] 0 0
Japan
State/province [17] 0 0
Aichi
Country [18] 0 0
Japan
State/province [18] 0 0
Fukuoka
Country [19] 0 0
Japan
State/province [19] 0 0
Fukuyama
Country [20] 0 0
Japan
State/province [20] 0 0
Gifu
Country [21] 0 0
Japan
State/province [21] 0 0
Tokyo
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Daegu
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Daehwa
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Seoul
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Ulsan
Country [26] 0 0
Latvia
State/province [26] 0 0
Riga
Country [27] 0 0
Netherlands
State/province [27] 0 0
Amsterdam
Country [28] 0 0
Netherlands
State/province [28] 0 0
Breda
Country [29] 0 0
Portugal
State/province [29] 0 0
Almada
Country [30] 0 0
Portugal
State/province [30] 0 0
Amadora
Country [31] 0 0
Portugal
State/province [31] 0 0
Lisbon
Country [32] 0 0
Saudi Arabia
State/province [32] 0 0
Riyadh
Country [33] 0 0
South Africa
State/province [33] 0 0
Johannesburg
Country [34] 0 0
Spain
State/province [34] 0 0
Barcelona
Country [35] 0 0
Spain
State/province [35] 0 0
Madrid
Country [36] 0 0
Turkey
State/province [36] 0 0
Istanbul
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Basildon
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Bournemouth
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Exeter
Country [40] 0 0
United Kingdom
State/province [40] 0 0
London
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Oxford
Country [42] 0 0
United Kingdom
State/province [42] 0 0
St Leonards

Funding & Sponsors
Primary sponsor type
Other
Name
Imperial College London
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02053038
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Justin ER Davies, MD
Address 0 0
Imperial College London
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02053038