Clinical trial NCT02053038: Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation
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
Overall status: UNKNOWN
Phase: NA
Conditions: Coronary Artery Disease
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2014-02-03
Enrollment: 2500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Major Adverse Cardiac Events
timeFrame: 30 days, 1, 2 and 5 years
Secondary outcomes:
measure: Death (all cause)
timeFrame: 30 days, 1, 2 and 5 years
measure: Death (cardiovascular)
timeFrame: 30 days, 1, 2 and 5 years
measure: Myocardial Infarction
timeFrame: 30 days, 1, 2 and 5 years
measure: Repeat revascularisation
timeFrame: 30 days, 1, 2 and 5 years
measure: Cost associated to iFR or FFR measurement
timeFrame: 30 days, 1, 2 and 5 years
measure: Quality of life assessed by EQ-5D-5L and Seattle Angina Questionnaire
timeFrame: 30 days, 1, 2 and 5 years
measure: Cost savings of removing secondary investigations
timeFrame: 30 days, 1, 2 and 5 years
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Arnold Seto
state: California
city: Lakewood
country: United States
facility: John Altman
state: Colorado
city: Atlanta
country: United States
facility: Habib Samady
state: Georgia
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Stony Brook
country: United States
facility: Allen Jeremias
state: New York
city: Durham
country: United States
facility: Manesh Patel
state: North Carolina
city: Adelaide
country: Australia
facility: Sam Lehman
city: Brisbane
country: Australia
facility: Darren Walters
city: Melbourne
country: Australia
facility: James Sapontis
city: Sydney
country: Australia
facility: Ravinay Bhindi
city: Antwerp
country: Belgium
facility: Christian Vrints
city: Bonheiden
country: Belgium
facility: Luc Janssens
city: Cairo
country: Egypt
facility: Ahmed Khashaba
city: Helsinki
country: Finland
facility: Mika Laine
city: Berlin
country: Germany
facility: Florian Krackhardt
city: Berlin
country: Germany
facility: Olaf Going
city: Koblenz
country: Germany
facility: Waldemar Bojara
city: Oldenburg
country: Germany
facility: Tobias Haerle
city: Catanzaro
country: Italy
facility: Ciro Indolfi
city: Rome
country: Italy
facility: Giampaolo Nicolli
city: Verona
country: Italy
facility: Flavio Ribichini
city: Aichi
country: Japan
facility: Hiroaki Takashima
city: Fukuoka
country: Japan
facility: Hiroyoshi Yokoi
city: Fukuyama
country: Japan
facility: Yuetsu Kikuta
city: Gifu
country: Japan
facility: Hitosh Matsuo
city: Tokyo
country: Japan
facility: Nob Tanaka
city: Daegu
country: Korea, Republic of
facility: Chang-Wook Nam
city: Daehwa
country: Korea, Republic of
facility: Joon-Hyung Doh
city: Seoul
country: Korea, Republic of
facility: Bon-Kwon Koo
city: Ulsan
country: Korea, Republic of
facility: Eun-Seok Shin
city: Riga
country: Latvia
facility: Andrejs Erglis
city: Amsterdam
country: Netherlands
facility: Jan Piek
city: Amsterdam
country: Netherlands
facility: Niels Van Royen
city: Breda
country: Netherlands
facility: Martijn Meuwissen
city: Almada
country: Portugal
facility: Hugo Vinhas
city: Amadora
country: Portugal
facility: Sergio Baptista
city: Lisbon
country: Portugal
facility: Pedro Canas Silva
city: Riyadh
country: Saudi Arabia
facility: Ali Alghamadi
city: Johannesburg
country: South Africa
facility: Farrel Hellig
city: Barcelona
country: Spain
facility: Salvatore Brugaletta
city: Madrid
country: Spain
facility: Clinico San Carlos
city: Madrid
country: Spain
facility: Eduardo Alegria
city: Istanbul
country: Turkey
facility: Murat Sezer
city: Basildon
country: United Kingdom
facility: Kare Tang
city: Bournemouth
country: United Kingdom
facility: Suneel Talwar
city: Exeter
country: United Kingdom
facility: Andrew Sharp
city: London
country: United Kingdom
facility: Imperial College London
city: London
country: United Kingdom
facility: Ranil De Silva
city: Oxford
country: United Kingdom
facility: Rajesh Kharbanda
city: St Leonards
country: United Kingdom
facility: Robert Gerber
Study officials:
affiliation: Imperial College London
name: Justin ER Davies, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinico San Carlos
name: Javier Escaned, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: Patrick Serruys, MD
role: STUDY_CHAIR
affiliation: Duke University
name: Manesh Patel, MD
role: STUDY_CHAIR
affiliation: Imperial College London
name: Sayan Sen, MD
role: STUDY_DIRECTOR
References:
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.
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.
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.