Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses (DEFINE-FLOW)

• ClinicalTrials.gov Identifier: NCT02328820
• Recruitment Status: Active, not recruiting
• First Posted: December 31, 2014
• Last Update Posted: January 17, 2019
• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Volcano Corporation
• Information provided by (Responsible Party): Nils Johnson, The University of Texas Health Science Center, Houston

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Other: Percutaneous coronary intervention (PCI); Other: Optimal medical therapy (OMT)	Not Applicable

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 455 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: DEFINE-FLOW (Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect - Combined Pressure and Doppler FLOW Velocity Measurements)
• Actual Study Start Date: October 2014
• Estimated Primary Completion Date: November 2019
• Estimated Study Completion Date: November 2019

Arms and Interventions

Arm	Intervention/treatment
All patients; All lesions undergo simultaneous assessment with a combined pressure and flow sensor	Other: Percutaneous coronary intervention (PCI); For lesions with both FFR<=0.8 and CFR<2.0; Other: Optimal medical therapy (OMT); For lesions with FFR>0.8 or CFR>=2.0 or both

Outcome Measures

Primary Outcome Measures :

1. Major adverse cardiac events [ Time Frame: 24 months ]
   All-cause death, non-fatal myocardial infarction, urgent and elective revascularization

Secondary Outcome Measures :

1. Angina (Canadian Cardiovascular Society (CCS) anginal class (or freedom from angina) [ Time Frame: 24 months ]
   Canadian Cardiovascular Society (CCS) anginal class (or freedom from angina)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Denmark

Aarhus University Hospital

Aarhus, Denmark

Italy

Catholic University of the Sacred Heart

Rome, Italy

Japan

Gifu Heart Center

Gifu, Japan

Toda Central General Hospital

Toda, Japan

Tokyo Medical University

Tokyo, Japan

Tsuchiura Kyodo

Tsuchiura, Japan

Netherlands

Amsterdam UMC - location AMC

Amsterdam, Netherlands

Amsterdam UMC - location VUmc

Amsterdam, Netherlands

Tergooi Hospital

Blaricum, Netherlands

Amphia Hospital

Breda, Netherlands

Spain

Hospital Clinico San Carlos

Madrid, Spain

United Kingdom

Royal Free Hospital

London, United Kingdom

Sponsors and Collaborators

The University of Texas Health Science Center, Houston

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Volcano Corporation

Investigators

• Principal Investigator: Nils Johnson, MD; University of Texas Medical School at Houston
• Study Director: Jan J Piek, MD, PhD; Academic Medical Center (AMC), Amsterdam

More Information

Publications:

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Matsumura M, Johnson NP, Fearon WF, Mintz GS, Stone GW, Oldroyd KG, De Bruyne B, Pijls NHJ, Maehara A, Jeremias A. Accuracy of Fractional Flow Reserve Measurements in Clinical Practice: Observations From a Core Laboratory Analysis. JACC Cardiovasc Interv. 2017 Jul 24;10(14):1392-1401. doi: 10.1016/j.jcin.2017.03.031.

Johnson NP, Gould KL, Di Carli MF, Taqueti VR. Invasive FFR and Noninvasive CFR in the Evaluation of Ischemia: What Is the Future? J Am Coll Cardiol. 2016 Jun 14;67(23):2772-2788. doi: 10.1016/j.jacc.2016.03.584. Review.

Gould KL, Johnson NP. Coronary Blood Flow After Acute MI: Alternative Truths. JACC Cardiovasc Interv. 2016 Mar 28;9(6):614-7. doi: 10.1016/j.jcin.2016.02.009.

Gould KL. Intense Exercise and Native Collateral Function in Stable Moderate Coronary Artery Disease: Incidental, Causal, or Clinically Important? Circulation. 2016 Apr 12;133(15):1431-4. doi: 10.1161/CIRCULATIONAHA.116.022037. Epub 2016 Mar 15.

Gould KL, Johnson NP. Myocardial Bridges: Lessons in Clinical Coronary Pathophysiology. JACC Cardiovasc Imaging. 2015 Jun;8(6):705-9. doi: 10.1016/j.jcmg.2015.02.013.

Gould KL, Johnson NP, Kaul S, Kirkeeide RL, Mintz GS, Rentrop KP, Sdringola S, Virmani R, Narula J. Patient selection for elective revascularization to reduce myocardial infarction and mortality: new lessons from randomized trials, coronary physiology, and statistics. Circ Cardiovasc Imaging. 2015 May;8(5). pii: e003099. doi: 10.1161/CIRCIMAGING.114.003099. Review.

• Responsible Party: Nils Johnson, Associate Professor of Medicine, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT02328820 History of Changes
• Other Study ID Numbers: HSC-MS-14-0442; NL48375.018.14 ( Other Identifier: Academic Medical Center (AMC), University of Amsterdam )
• First Posted: December 31, 2014
• Last Update Posted: January 17, 2019
• Last Verified: January 2019

Keywords provided by Nils Johnson, The University of Texas Health Science Center, Houston:

Fractional Flow Reserve, Myocardial; Coronary Flow Reserve

Additional relevant MeSH terms:

Coronary Artery Disease; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases