Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses

NCT02328820 | Completed DMC

• 2 other identifiers: HSC-MS-14-0442NL48375.018.14
• Study Type: interventional
• Target: 455
• Locations: 6 countries
• Sites: 12

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).

Conditions

Coronary Artery Disease

Keywords

Fractional Flow Reserve, Myocardial; Coronary Flow Reserve

Outcome Measures

Primary Outcomes (1)

• Major adverse cardiac events

  All-cause death, non-fatal myocardial infarction, urgent and elective revascularization

  24 months

Secondary Outcomes (1)

• Angina (Canadian Cardiovascular Society (CCS) anginal class (or freedom from angina)

  24 months

Study Arms (1)

All patients

OTHER

All lesions undergo simultaneous assessment with a combined pressure and flow sensor

Other: Percutaneous coronary intervention (PCI); Other: Optimal medical therapy (OMT)

Interventions

Percutaneous coronary intervention (PCI) OTHER

For lesions with both FFR\<=0.8 and CFR\<2.0

All patients

Optimal medical therapy (OMT) OTHER

For lesions with FFR\>0.8 or CFR\>=2.0 or both

All patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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).
• 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.

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Volcano Corporation: collaborator

Study Sites (12)

Aarhus University Hospital

Aarhus, Denmark

Location

Catholic University of the Sacred Heart

Rome, Italy

Location

Gifu Heart Center

Gifu, Japan

Location

Toda Central General Hospital

Toda, Japan

Location

Tokyo Medical University

Tokyo, Japan

Location

Tsuchiura Kyodo

Tsuchiura, Japan

Location

Amsterdam UMC - location AMC

Amsterdam, Netherlands

Location

Amsterdam UMC - location VUmc

Amsterdam, Netherlands

Location

Tergooi Hospital

Blaricum, Netherlands

Location

Amphia Hospital

Breda, Netherlands

Location

Hospital Clinico San Carlos

Madrid, Spain

Location

Royal Free Hospital

London, United Kingdom

Location

Related Publications (18)

• 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.

  PMID: 22340827 BACKGROUND

• 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.

  PMID: 24782198 BACKGROUND

• Tas A, Alan Y, Tas IK, Aydin OE, Atay Z, Yilmaz S, Ozcan A, van de Hoef TP, Umman S, Piek Md JJ, Sezer M. Coronary Microvascular Dysfunction Alters the Pulsatile Behavior of the Resting Coronary Blood Flow. Microcirculation. 2025 Aug;32(6):e70021. doi: 10.1111/micc.70021.

  PMID: 40831095 DERIVED

• Tas A, Alan Y, Kara Tas I, Umman S, Parker KH, van de Hoef TP, Sezer M, Piek JJ. The impact of high microvascular resistance on coronary wave energetics depends on coronary microvascular functionality. Eur Heart J Open. 2025 May 5;5(3):oeaf050. doi: 10.1093/ehjopen/oeaf050. eCollection 2025 May.

  PMID: 40417173 DERIVED

• Tas A, Alan Y, Muftuogullari A, Haj Mohammad AIM, Umman S, Parker KH, Sezer M. Coronary microvascular dysfunction and autoregulatory capacity interfere with resting Dicrotic notch morphology. Microvasc Res. 2025 Jan;157:104750. doi: 10.1016/j.mvr.2024.104750. Epub 2024 Sep 30.

  PMID: 39357645 DERIVED

• Achim A, Johnson NP, Liblik K, Burckhardt A, Krivoshei L, Leibundgut G. Coronary steal: how many thieves are out there? Eur Heart J. 2023 Aug 7;44(30):2805-2814. doi: 10.1093/eurheartj/ehad327.

  PMID: 37264699 DERIVED

• van de Hoef TP, Stegehuis VE, Madera-Cambero MI, van Royen N, van der Hoeven NW, de Waard GA, Meuwissen M, Christiansen EH, Eftekhari A, Niccoli G, Lockie T, Matsuo H, Nakayama M, Kakuta T, Tanaka N, Casadonte L, Spaan JAE, Siebes M, Tijssen JGP, Escaned J, Piek JJ. Impact of core laboratory assessment on treatment decisions and clinical outcomes using combined fractional flow reserve and coronary flow reserve measurements - DEFINE-FLOW core laboratory sub-study. Int J Cardiol. 2023 Apr 15;377:9-16. doi: 10.1016/j.ijcard.2023.01.009. Epub 2023 Jan 11.

  PMID: 36640965 DERIVED

• 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.

  PMID: 35410913 DERIVED

• 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.

  PMID: 34503740 DERIVED

• 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.

  PMID: 32660310 DERIVED

• 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.

  PMID: 32062172 DERIVED

• 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.

  PMID: 30115688 DERIVED

• 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.

  PMID: 28728652 DERIVED

• 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.

  PMID: 27282899 DERIVED

• 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.

  PMID: 27013162 DERIVED

• 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.

  PMID: 26979084 DERIVED

• 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.

  PMID: 26068287 DERIVED

• 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.

  PMID: 25977304 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Percutaneous Coronary Intervention

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Endovascular Procedures; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Study Officials

• Nils Johnson, MD

  University of Texas Medical School at Houston

  PRINCIPAL INVESTIGATOR

• Jan J Piek, MD, PhD

  Academic Medical Center (AMC), Amsterdam

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: December 31, 2014
• Study Start: October 1, 2014
• Primary Completion: November 1, 2019
• Study Completion: April 1, 2021
• Last Updated: April 6, 2021

Record last verified: 2021-04

Locations

ES (1); GB (1); DK (1); IT (1); JP (4); NL (4)