Ignite Creation Date:
2025-12-25 @ 3:37 AM
Ignite Modification Date:
2025-12-26 @ 2:20 AM
Study NCT ID:
NCT04048005
Status:
UNKNOWN
Last Update Posted:
2019-08-07
First Post:
2019-08-04
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Relationship Between Fractional Flow Reserve/ Instantaneous Wave Free Ratio and Endothelial Wall Shear Stress
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D060050', 'term': 'Angina, Stable'}, {'id': 'D054058', 'term': 'Acute Coronary Syndrome'}, {'id': 'D003324', 'term': 'Coronary Artery Disease'}], 'ancestors': [{'id': 'D000787', 'term': 'Angina Pectoris'}, {'id': 'D017202', 'term': 'Myocardial Ischemia'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002637', 'term': 'Chest Pain'}, {'id': 'D010146', 'term': 'Pain'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D003327', 'term': 'Coronary Disease'}, {'id': 'D001161', 'term': 'Arteriosclerosis'}, {'id': 'D001157', 'term': 'Arterial Occlusive Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D053805', 'term': 'Fractional Flow Reserve, Myocardial'}], 'ancestors': [{'id': 'D003326', 'term': 'Coronary Circulation'}, {'id': 'D001775', 'term': 'Blood Circulation'}, {'id': 'D002320', 'term': 'Cardiovascular Physiological Phenomena'}, {'id': 'D002943', 'term': 'Circulatory and Respiratory Physiological Phenomena'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'RETROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 200}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2017-01-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-08', 'completionDateStruct': {'date': '2020-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2019-08-06', 'studyFirstSubmitDate': '2019-08-04', 'studyFirstSubmitQcDate': '2019-08-06', 'lastUpdatePostDateStruct': {'date': '2019-08-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-08-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Wall shear stress (WSS) / Fractional flow reserve (FFR) or instantaneous wave free ratio (iFR)correlation', 'timeFrame': 'WSS will be calculated after 3D coronary reconstruction, within one year after the completion of retrospective enrollement', 'description': 'After 3-dimensional coronary reconstruction through dedicated software (Qangio XA 3D (MEDIS), WSS will be calculated through fluydodinamic equations across the entire coronary vessel and across coronary stenosis. WSS values predicting positive invasive FFR and iFR (according to their dichothomic established values of positivity, namely FFR \\< 0.8 and iFR \\< 0.89) measurements will be searched, along with any possible relationship between WSS and FFR/iFR as continuos values.'}, {'measure': 'MACE (major adverse cardiovascular events)', 'timeFrame': 'MACE will be evaluated for each patients through study completion, an average of 1 year', 'description': 'The association of regional WSS with major cardiovascular adverse events at available follow-up will be further evaluated to assess if lesion-level WSS might predict overall patient-level outcomes'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Stable Angina', 'Acute Coronary Syndrome', 'Coronary Artery Disease']}, 'referencesModule': {'references': [{'pmid': '29268883', 'type': 'BACKGROUND', 'citation': 'Ford TJ, Berry C, De Bruyne B, Yong ASC, Barlis P, Fearon WF, Ng MKC. Physiological Predictors of Acute Coronary Syndromes: Emerging Insights From the Plaque to the Vulnerable Patient. JACC Cardiovasc Interv. 2017 Dec 26;10(24):2539-2547. doi: 10.1016/j.jcin.2017.08.059.'}, {'pmid': '21788584', 'type': 'BACKGROUND', 'citation': 'Samady H, Eshtehardi P, McDaniel MC, Suo J, Dhawan SS, Maynard C, Timmins LH, Quyyumi AA, Giddens DP. Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease. Circulation. 2011 Aug 16;124(7):779-88. doi: 10.1161/CIRCULATIONAHA.111.021824. Epub 2011 Jul 25.'}, {'pmid': '25323250', 'type': 'BACKGROUND', 'citation': 'Johnson NP, Toth GG, Lai D, Zhu H, Acar G, Agostoni P, Appelman Y, Arslan F, Barbato E, Chen SL, Di Serafino L, Dominguez-Franco AJ, Dupouy P, Esen AM, Esen OB, Hamilos M, Iwasaki K, Jensen LO, Jimenez-Navarro MF, Katritsis DG, Kocaman SA, Koo BK, Lopez-Palop R, Lorin JD, Miller LH, Muller O, Nam CW, Oud N, Puymirat E, Rieber J, Rioufol G, Rodes-Cabau J, Sedlis SP, Takeishi Y, Tonino PA, Van Belle E, Verna E, Werner GS, Fearon WF, Pijls NH, De Bruyne B, Gould KL. Prognostic value of fractional flow reserve: linking physiologic severity to clinical outcomes. J Am Coll Cardiol. 2014 Oct 21;64(16):1641-54. doi: 10.1016/j.jacc.2014.07.973.'}, {'pmid': '22924638', 'type': 'BACKGROUND', 'citation': 'De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PA, Piroth Z, Jagic N, Mobius-Winkler S, Rioufol G, Witt N, Kala P, MacCarthy P, Engstrom T, Oldroyd KG, Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Juni P, Fearon WF; FAME 2 Trial Investigators. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012 Sep 13;367(11):991-1001. doi: 10.1056/NEJMoa1205361. Epub 2012 Aug 27.'}, {'pmid': '30596995', 'type': 'BACKGROUND', 'citation': 'Zimmermann FM, Omerovic E, Fournier S, Kelbaek H, Johnson NP, Rothenbuhler M, Xaplanteris P, Abdel-Wahab M, Barbato E, Hofsten DE, Tonino PAL, Boxma-de Klerk BM, Fearon WF, Kober L, Smits PC, De Bruyne B, Pijls NHJ, Juni P, Engstrom T. Fractional flow reserve-guided percutaneous coronary intervention vs. medical therapy for patients with stable coronary lesions: meta-analysis of individual patient data. Eur Heart J. 2019 Jan 7;40(2):180-186. doi: 10.1093/eurheartj/ehy812.'}, {'pmid': '29785878', 'type': 'BACKGROUND', 'citation': 'Xaplanteris P, Fournier S, Pijls NHJ, Fearon WF, Barbato E, Tonino PAL, Engstrom T, Kaab S, Dambrink JH, Rioufol G, Toth GG, Piroth Z, Witt N, Frobert O, Kala P, Linke A, Jagic N, Mates M, Mavromatis K, Samady H, Irimpen A, Oldroyd K, Campo G, Rothenbuhler M, Juni P, De Bruyne B; FAME 2 Investigators. Five-Year Outcomes with PCI Guided by Fractional Flow Reserve. N Engl J Med. 2018 Jul 19;379(3):250-259. doi: 10.1056/NEJMoa1803538. Epub 2018 May 22.'}, {'pmid': '29406855', 'type': 'BACKGROUND', 'citation': 'Driessen RS, Stuijfzand WJ, Raijmakers PG, Danad I, Min JK, Leipsic JA, Ahmadi A, Narula J, van de Ven PM, Huisman MC, Lammertsma AA, van Rossum AC, van Royen N, Knaapen P. Effect of Plaque Burden and Morphology on Myocardial Blood Flow and Fractional Flow Reserve. J Am Coll Cardiol. 2018 Feb 6;71(5):499-509. doi: 10.1016/j.jacc.2017.11.054.'}, {'pmid': '30309470', 'type': 'BACKGROUND', 'citation': 'Kumar A, Thompson EW, Lefieux A, Molony DS, Davis EL, Chand N, Fournier S, Lee HS, Suh J, Sato K, Ko YA, Molloy D, Chandran K, Hosseini H, Gupta S, Milkas A, Gogas B, Chang HJ, Min JK, Fearon WF, Veneziani A, Giddens DP, King SB 3rd, De Bruyne B, Samady H. High Coronary Shear Stress in Patients With Coronary Artery Disease Predicts Myocardial Infarction. J Am Coll Cardiol. 2018 Oct 16;72(16):1926-1935. doi: 10.1016/j.jacc.2018.07.075.'}, {'pmid': '27522378', 'type': 'BACKGROUND', 'citation': 'Lee KE, Kim GT, Lee JS, Chung JH, Shin ES, Shim EB. A patient-specific virtual stenotic model of the coronary artery to analyze the relationship between fractional flow reserve and wall shear stress. Int J Cardiol. 2016 Nov 1;222:799-805. doi: 10.1016/j.ijcard.2016.07.153. Epub 2016 Aug 3.'}]}, 'descriptionModule': {'briefSummary': 'This study, designed as a retrospective registry, aims to investigate the relationship and potential interplay between fractional flow reserve (FFR) or instantaneous waves free ratio (iFR) with wall shear stress (WSS) in the context of intermediate coronary stenosis.', 'detailedDescription': "BACKGROUND AND RATIONALE Despite great advances in atherothrombosis science, the complex interplay of factors leading to plaque progression remains elusive. Specifically, the dynamics leading a stable plaque towards rupture and over imposed thrombosis are largely speculative. Wall shear stress (WSS), the mechanical force elicited by blood flow on the vessel walls, is emerging as a potent trigger of bio-humoral processes eventually leading to endothelial damage, plaque progression and destabilization.\n\nFractional flow reserve (FFR), assessing the aggregate hemodynamical significance of a stenosis on the subtended myocardium, stratifies the risk of major adverse cardiovascular events and reduces their occurrence when used to guide revascularization. While this event reduction is mainly driven by ischemia-caused urgent revascularization, it is emerging that FFR-guided revascularization may also reduce myocardial infarction.\n\nWhile the physiological relationship between a lesion's FFR and resulting ischemia in the subtended myocardium is intuitive, the mechanisms linking FFR to atherothrombosis are less clearly defined.\n\nLesions with lower FFR are associated with adverse atherosclerotic plaque characteristics (APCs), however, the causative nexus of this relationship is not well established. It has been proposed both that the physiological base for this relation underlies in disturbed lesion hemodynamics, occurring at a greater extent as the degree of functional obstruction increases (i.e. FFR reduction drives APCs), and that APCs directly impair the vessel's vasodilatory reserve resulting in detrimental hyperemic perfusion (i.e. APCs drive FFR reduction).\n\nWSS measures the regional tangential hemodynamic forces produced by viscous blood flow on the endothelium, which is established drivers of plaque progression and transformation toward an adverse plaque phenotype. Intriguingly, WSS may thus represent the missing link between FFR and atherothrombosis.\n\nFew studies have focused on the interplay of FFR and WSS and the provided results are inconclusive (9, 10). This relation remains thus to be fully characterized.\n\nThis study will investigate the association of aggregate with regional hemodynamic forces as defined by the lesion-level relation of FFR or instantaneous wave-free ratio (iFR) and regional WSS across the lesion.\n\nSTUDY DESIGN This is a retrospective observational multi-center study, including consecutive patients who underwent coronary angiography at for symptom/ischemia-driven, suspected stable coronary artery disease or for acute coronary syndromes (ACS) with evidence of at least one lesion with 30-90% diameter-stenosis, that underwent subsequent iFR/FFR assessment.\n\nCoronary angiography of the screened patients will be retrospectively evaluated by an experienced Interventional cardiologist and, if deemed suitable for baseline angiographic reconstruction will be included in this registry.\n\n3-dimensional (3D) geometric reconstructions of each patient's target vessel will be created by using end-diastolic angiographic projections at least 25° apart. Computational fluid dynamics models will be applied to derive regional WSS values across the stenosis.\n\nClinical baseline characteristics and angiographic features obtained by visual and functional assessment, and 3-D reconstruction and computation, along with major adverse cardiovascular events, will be collected in a dedicated electronic form.\n\nThe analysts performing angiographic 3-D reconstruction and WSS computations will be blinded to FFR/iFR values and clinical data.\n\nSTUDY ENDPOINTS This study will investigate the association of aggregate and regional hemodynamic forces as established by the lesion-level relation of FFR/iFR with regional WSS across the lesion.\n\nThe association of regional WSS with major cardiovascular adverse events at available follow-up will be further evaluated to assess if lesion-level WSS might predict overall patient-level outcomes (in case of more than one lesion for a single patient, the lesion with the highest WSS will be considered for this analysis)."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '90 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': "\\- The study will include any patient referred for coronary angiography at each involved center and with a subsequent invasive physiological assessment performed with FFR or iFR (or both) at operating physician's discretion on intermediate coronary stenosis (diameter of stenosis ranging from 30-90% at visual angiographic estimation).", 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Angiography performed for suspected symptom/ischemia-driven stable coronary artery disease or for acute coronary syndromes\n* At least one lesion with 30-90% diameter stenosis at invasive angiography with FFR/iFR assessed (for patients with acute coronary syndromes, the invasive assessment will be performed on non-culprit stenosis\n* Patient informed consent for data collection and publication in anonymous studies\n\nExclusion Criteria:\n\n* Quality of angiographic frames not sufficient for 3D-reconstruction and/or computations\n* Patients denying informed consent'}, 'identificationModule': {'nctId': 'NCT04048005', 'acronym': 'RELATE', 'briefTitle': 'Relationship Between Fractional Flow Reserve/ Instantaneous Wave Free Ratio and Endothelial Wall Shear Stress', 'organization': {'class': 'OTHER', 'fullName': 'A.O.U. Città della Salute e della Scienza'}, 'officialTitle': 'RELATionship bEtween Lesion-level Invasive Fractional Flow Reserve AND Endothelial Wall Shear Stress the RELATE FFR and WSS Study', 'orgStudyIdInfo': {'id': 'RELATE FFR and WSS'}}, 'armsInterventionsModule': {'interventions': [{'name': 'Fractional flow reserve', 'type': 'DIAGNOSTIC_TEST', 'otherNames': ['instantaneous wave free ratio']}]}, 'contactsLocationsModule': {'locations': [{'zip': '10098', 'city': 'Rivoli', 'status': 'ENROLLING_BY_INVITATION', 'country': 'Italy', 'facility': 'Ospedale di Rivoli', 'geoPoint': {'lat': 45.07073, 'lon': 7.51465}}, {'zip': '10126', 'city': 'Torino', 'status': 'RECRUITING', 'country': 'Italy', 'contacts': [{'name': "Fabrizio D'Ascenzo, MD", 'role': 'CONTACT', 'email': 'fabrizio.dascenzo@gmail.com', 'phone': '+390116336023'}], 'facility': 'AOU Città della Salute e della Scienza di Torino', 'geoPoint': {'lat': 44.88856, 'lon': 11.99138}}, {'zip': '10144', 'city': 'Torino', 'status': 'ENROLLING_BY_INVITATION', 'country': 'Italy', 'facility': 'Ospedale San Giovanni Bosco', 'geoPoint': {'lat': 44.88856, 'lon': 11.99138}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'A.O.U. Città della Salute e della Scienza', 'class': 'OTHER'}, 'collaborators': [{'name': 'Politecnico di Torino', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Medical Doctor', 'investigatorFullName': "Fabrizio D'Ascenzo", 'investigatorAffiliation': 'A.O.U. Città della Salute e della Scienza'}}}}