Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses

Coronary Artery Disease Clinical Trial

— DEFINE-FLOW  

Official title:

DEFINE-FLOW (Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect - Combined Pressure and Doppler FLOW Velocity Measurements)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02328820
• Other study ID #: HSC-MS-14-0442
• Secondary ID: NL48375.018.14
• Status: Completed
• Phase: N/A
• Start date: October 2014
• Est. completion date: April 2021

Study information

• Verified date: April 2021
• Source: The University of Texas Health Science Center, Houston
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the prognostic value and therapeutic potential of combined pressure and flow measurements when evaluating a coronary artery stenosis. Lesions with intact coronary flow reserve (CFR) despite a reduced fractional flow reserve (FFR) will receive optimal medical therapy. Only lesions with a simultaneous reduction in both CFR and FFR will be treated with percutaneous coronary intervention (PCI).

Description:

Pressure and flow represent the two physiologic variables that can be measured directly inside a coronary artery. Already pressure measurements have proven their clinical value in the form of fractional flow reserve (FFR). However, myocardial function can remain intact with sufficient flow, even at a low perfusion pressure. Therefore, combined pressure and flow measurements provide a more complete description of physiologic stenosis severity as a guide to medical treatment versus revascularization. Based on existing work relating the most common flow measurement, coronary flow reserve (CFR), to FFR and linking both variables with subsequent prognosis, we hypothesize that lesions with an intact CFR>=2.0 can be reasonably treated with medical therapy despite a reduced FFR<=0.8.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 455
• Est. completion date: April 2021
• Est. primary completion date: November 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years.

• Eligible for PCI based on local practice standards during the current procedure (PCI cannot be staged).

• At least one epicardial stenosis of =50% diameter (by visual or quantitative assessment) and meeting the following criteria as determined by the operator based on either a prior or the current diagnostic angiogram:

• <100% diameter (not a chronic, total occlusion);

• in a native coronary artery (including side branches but excludes bypass grafts);

• of =2.5mm reference diameter (near the level of the stenosis);

• and supplies sufficiently viable myocardium (exclude regions of known, prior, transmural myocardial infarction).

• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Anatomic exclusions:

• Prior CABG.

• Preferred treatment strategy for revascularization would be CABG based on local practice standards.

• Left main coronary artery disease requiring revascularization.

• Extremely tortuous or calcified coronary arteries precluding intracoronary physiologic measurements. Operators may also exclude subtotal or similar high-grade lesions, which in their judgment may be threatened by ComboWire placement.

• Known severe LV hypertrophy (septal wall thickness at echocardiography of >13 mm).

• Clinical exclusions:

• Inability to receive intravenous adenosine (for example, severe reactive airway disease, marked hypotension, or high-grade AV block without pacemaker).

• Recent (within 3 weeks prior to cardiac catheterization) ST-segment elevation myocardial infarction (STEMI) in any arterial distribution (not specifically target lesion).

• Culprit lesions (based on clinical judgment of the operator) for either STEMI or non-STEMI cannot be included.

• Severe cardiomyopathy (LV ejection fraction <30%).

• Planned need for cardiac surgery (for example, valve surgery, treatment of aortic aneurysm, or septal myomectomy).

• General exclusions:

• A life expectancy of less than 2 years.

• Inability to sign an informed consent, due to any mental condition that renders the subject unable to understand the nature, scope, and possible consequences of the trial or due to mental retardation or language barrier.

• Potential for non-compliance towards the requirements for follow-up visits.

• Participation or planned participation in another cardiovascular clinical trial before completing the 24 month follow-up.

Related Conditions & MeSH terms

• Coronary Artery Disease

Intervention

Other:
• Percutaneous coronary intervention (PCI)
For lesions with both FFR<=0.8 and CFR<2.0
• Optimal medical therapy (OMT)
For lesions with FFR>0.8 or CFR>=2.0 or both

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus
Italy	Catholic University of the Sacred Heart	Rome
Japan	Gifu Heart Center	Gifu
Japan	Toda Central General Hospital	Toda
Japan	Tokyo Medical University	Tokyo
Japan	Tsuchiura Kyodo	Tsuchiura
Netherlands	Amsterdam UMC - location AMC	Amsterdam
Netherlands	Amsterdam UMC - location VUmc	Amsterdam
Netherlands	Tergooi Hospital	Blaricum
Netherlands	Amphia Hospital	Breda
Spain	Hospital Clinico San Carlos	Madrid
United Kingdom	Royal Free Hospital	London

Sponsors (3)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Volcano Corporation

Countries where clinical trial is conducted

Denmark,  Italy,  Japan,  Netherlands,  Spain,  United Kingdom, 

References & Publications (2)

Johnson NP, Kirkeeide RL, Gould KL. Is discordance of coronary flow reserve and fractional flow reserve due to methodology or clinically relevant coronary pathophysiology? JACC Cardiovasc Imaging. 2012 Feb;5(2):193-202. doi: 10.1016/j.jcmg.2011.09.020. — View Citation

van de Hoef TP, van Lavieren MA, Damman P, Delewi R, Piek MA, Chamuleau SA, Voskuil M, Henriques JP, Koch KT, de Winter RJ, Spaan JA, Siebes M, Tijssen JG, Meuwissen M, Piek JJ. Physiological basis and long-term clinical outcome of discordance between fractional flow reserve and coronary flow velocity reserve in coronary stenoses of intermediate severity. Circ Cardiovasc Interv. 2014 Jun;7(3):301-11. doi: 10.1161/CIRCINTERVENTIONS.113.001049. Epub 2014 Apr 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major adverse cardiac events	All-cause death, non-fatal myocardial infarction, urgent and elective revascularization	24 months
Secondary	Angina (Canadian Cardiovascular Society (CCS) anginal class (or freedom from angina)	Canadian Cardiovascular Society (CCS) anginal class (or freedom from angina)	24 months