Clinical trial NCT02328820: Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses
Official title: DEFINE-FLOW (Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect - Combined Pressure and Doppler FLOW Velocity Measurements)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Disease
Keywords: Fractional Flow Reserve, Myocardial
Coronary Flow Reserve
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Volcano Corporation
First posted: 2014-12-31
Enrollment: 455
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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).

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.

Eligibility 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.

Primary outcomes:
measure: Major adverse cardiac events
timeFrame: 24 months
Secondary outcomes:
measure: Angina (Canadian Cardiovascular Society (CCS) anginal class (or freedom from angina)
timeFrame: 24 months
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Rome
country: Italy
facility: Catholic University of the Sacred Heart
city: Gifu
country: Japan
facility: Gifu Heart Center
city: Toda
country: Japan
facility: Toda Central General Hospital
city: Tokyo
country: Japan
facility: Tokyo Medical University
city: Tsuchiura
country: Japan
facility: Tsuchiura Kyodo
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - location AMC
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - location VUmc
city: Blaricum
country: Netherlands
facility: Tergooi Hospital
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: University of Texas Medical School at Houston
name: Nils Johnson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Academic Medical Center (AMC), Amsterdam
name: Jan J Piek, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
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.
citation: Eftekhari A, Westra J, Stegehuis V, Holm NR, van de Hoef TP, Kirkeeide RL, Piek JJ, Lance Gould K, Johnson NP, Christiansen EH. Prognostic value of microvascular resistance and its association to fractional flow reserve: a DEFINE-FLOW substudy. Open Heart. 2022 Apr;9(1):e001981. doi: 10.1136/openhrt-2022-001981.
citation: Johnson NP, Collet C. Can FFR After Stenting Help Reduce Target Vessel Failure? JACC Cardiovasc Interv. 2021 Sep 13;14(17):1901-1903. doi: 10.1016/j.jcin.2021.08.001. No abstract available.
citation: Murai T, Stegehuis VE, van de Hoef TP, Wijntjens GWM, Hoshino M, Kanaji Y, Sugiyama T, Hamaya R, Nijjer SS, de Waard GA, Echavarria-Pinto M, Knaapen P, Meuwissen M, Davies JE, van Royen N, Escaned J, Siebes M, Kirkeeide RL, Gould KL, Johnson NP, Piek JJ, Kakuta T. Coronary Flow Capacity to Identify Stenosis Associated With Coronary Flow Improvement After Revascularization: A Combined Analysis From DEFINE FLOW and IDEAL. J Am Heart Assoc. 2020 Jul 21;9(14):e016130. doi: 10.1161/JAHA.120.016130. Epub 2020 Jul 14.
citation: Stegehuis VE, Wijntjens GWM, van de Hoef TP, Casadonte L, Kirkeeide RL, Siebes M, Spaan JAE, Gould KL, Johnson NP, Piek JJ. Distal Evaluation of Functional performance with Intravascular sensors to assess the Narrowing Effect-combined pressure and Doppler FLOW velocity measurements (DEFINE-FLOW) trial: Rationale and trial design. Am Heart J. 2020 Apr;222:139-146. doi: 10.1016/j.ahj.2019.08.018. Epub 2019 Sep 1.
citation: Gould KL, Johnson NP, Roby AE, Nguyen T, Kirkeeide R, Haynie M, Lai D, Zhu H, Patel MB, Smalling R, Arain S, Balan P, Nguyen T, Estrera A, Sdringola S, Madjid M, Nascimbene A, Loyalka P, Kar B, Gregoric I, Safi H, McPherson D. Regional, Artery-Specific Thresholds of Quantitative Myocardial Perfusion by PET Associated with Reduced Myocardial Infarction and Death After Revascularization in Stable Coronary Artery Disease. J Nucl Med. 2019 Mar;60(3):410-417. doi: 10.2967/jnumed.118.211953. Epub 2018 Aug 16.
citation: 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.
citation: 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.
citation: 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. No abstract available.
citation: 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. No abstract available.
citation: 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. No abstract available.
citation: 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):e003099. doi: 10.1161/CIRCIMAGING.114.003099. No abstract available.