Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation

Coronary Artery Disease Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02053038
• Other study ID #: 13SM1797
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 2014
• Est. completion date: January 19, 2021

Study information

• Verified date: August 2019
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2500
• Est. completion date: January 19, 2021
• Est. primary completion date: January 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Device:
• iFR
Treatment guided by instantaneous wave-free ratio
• FFR
Treatment guided by Fractional Flow Reserve

Locations

Country	Name	City	State
Australia	Sam Lehman	Adelaide
Australia	Darren Walters	Brisbane
Australia	James Sapontis	Melbourne
Australia	Ravinay Bhindi	Sydney
Belgium	Christian Vrints	Antwerp
Belgium	Luc Janssens	Bonheiden
Egypt	Ahmed Khashaba	Cairo
Finland	Mika Laine	Helsinki
Germany	Florian Krackhardt	Berlin
Germany	Olaf Going	Berlin
Germany	Waldemar Bojara	Koblenz
Germany	Tobias Haerle	Oldenburg
Italy	Ciro Indolfi	Catanzaro
Italy	Giampaolo Nicolli	Rome
Italy	Flavio Ribichini	Verona
Japan	Hiroaki Takashima	Aichi
Japan	Hiroyoshi Yokoi	Fukuoka
Japan	Yuetsu Kikuta	Fukuyama
Japan	Hitosh Matsuo	Gifu
Japan	Nob Tanaka	Tokyo
Korea, Republic of	Chang-Wook Nam	Daegu
Korea, Republic of	Joon-Hyung Doh	Daehwa
Korea, Republic of	Bon-Kwon Koo	Seoul
Korea, Republic of	Eun-Seok Shin	Ulsan
Latvia	Andrejs Erglis	Riga
Netherlands	Jan Piek	Amsterdam
Netherlands	Niels Van Royen	Amsterdam
Netherlands	Martijn Meuwissen	Breda
Portugal	Hugo Vinhas	Almada
Portugal	Sergio Baptista	Amadora
Portugal	Pedro Canas Silva	Lisbon
Saudi Arabia	Ali Alghamadi	Riyadh
South Africa	Farrel Hellig	Johannesburg
Spain	Salvatore Brugaletta	Barcelona
Spain	Clinico San Carlos	Madrid
Spain	Eduardo Alegria	Madrid
Turkey	Murat Sezer	Istanbul
United Kingdom	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 States	Habib Samady	Atlanta	Georgia
United States	Manesh Patel	Durham	North Carolina
United States	John Altman	Lakewood	Colorado
United States	Arnold Seto	Long Beach	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Allen Jeremias	Stony Brook	New York

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Egypt,  Finland,  Germany,  Italy,  Japan,  Korea, Republic of,  Latvia,  Netherlands,  Portugal,  Saudi Arabia,  South Africa,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major Adverse Cardiac Events	Composite of death, myocardial infarction, unplanned revascularisation	30 days, 1, 2 and 5 years
Secondary	Death (all cause)		30 days, 1, 2 and 5 years
Secondary	Death (cardiovascular)		30 days, 1, 2 and 5 years
Secondary	Myocardial Infarction		30 days, 1, 2 and 5 years
Secondary	Repeat revascularisation		30 days, 1, 2 and 5 years
Secondary	Cost associated to iFR or FFR measurement	Cost associated to iFR or FFR	30 days, 1, 2 and 5 years
Secondary	Quality of life assessed by EQ-5D-5L and Seattle Angina Questionnaire		30 days, 1, 2 and 5 years
Secondary	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.	30 days, 1, 2 and 5 years