Comparison of Optical Coherence Tomography-derived Minimal Lumen Area, Invasive Fractional Flow Reserve and FFRCT

Coronary Stenosis Clinical Trial

— OPTICO-LM  

Official title:

Multimodality Assessment of Intermediate Left Main Stenosis: Comparison of Optical Coherence Tomography-derived Minimal Lumen Area, Invasive Fractional Flow Reserve and FFRCT

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03820492
• Other study ID #: OPTICO-LM
• Status: Recruiting
• Phase: N/A
• Start date: May 28, 2019
• Est. completion date: December 31, 2026

Study information

• Verified date: February 2023
• Source: University Hospital Inselspital, Berne
• Contact: Lorenz Raeber, Prof. MD PhD
• Phone: +41316322111
• Email: lorenz.raeber[@]insel.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Significant left main (LM) stenosis is associated with a poor prognosis, therefore, adequate judgement of the prognostic significance of LM stenosis is essential to improve patients' prognosis. Recently, fractional flow reserve (FFR) has become widespread practice and carries a Class Ia recommendation to assess functional significance of intermediate coronary stenosis in patients with stable angina. Intravascular ultrasound (IVUS)-derived minimum lumen area (MLA) represents an accurate measure to determine LM significance as shown in multiple studies, while optical coherence tomography (OCT) ,which is a novel intracoronary imaging method with a greater spatial resolution (15μm vs. 100μm), faster image acquisition and facilitated image interpretation, OCT derived-MLA has never been validated against FFR and accordingly, it is not mentioned in the current guidelines for myocardial revascularization. Coronary computed tomography angiography (CTA) has emerged as a noninvasive alternative of coronary angiography with its excellent negative predictive value, while the positive predictive value of CTA is limited. Computational fluid dynamics is an emerging method that enables prediction of blood flow in coronary arteries and calculation of FFR from computed tomography (FFRCT) noninvasively. Noninvasive and accurate assessment of functional significance would bring a great benefit for patients with LM stenosis, however, there are no data to evaluate the diagnostic accuracy of FFRCT for LM stenosis in comparison with FFR and minimal lumen area derived by OCT.

This study will investigate the optimal OCT-derived MLA cut-off point and the diagnostic performance of FFRCT for intermediate LM stenosis compared with FFR ≤0.8 as a reference standard.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 104
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Unprotected LM lesion [midshaft, and distal bifurcation (Medina 1,1,1 or 1,1,0 or 1,0,1 or 1,0,0)] of 30% to 80% angiographic diameter stenosis (DS) on visual estimation or equivocal disease by angiography.

• Age =18 years.

• Ability to give preliminary oral consent witnessed by an independent physician or sign written informed consent prior to any study-specific procedures.

Exclusion Criteria:

• Significant distal lesions (>50% angiographic DS on visual estimation within the left anterior descending artery [LAD] or left circumflex artery [LCX], except for ostium of LAD or LCX or diseased side branch [e.g. diagonal branch, obtuse marginal branch])

• Ostial LM disease.

• Acute coronary syndrome (ACS) (non-ST-elevation ACS and ST-elevation MI).

• LM In-stent restenosis.

• Previous coronary stenting of the left coronary system.

• Chronic total occlusion.

• Previous coronary artery bypass graft.

• Previous MI related to the left coronary artery.

• Occurrence of ventricularization or hypotension during engagement of the LM ostial lesion.

• The presence of hemodynamic instability.

• Known renal insufficiency (serum creatinine >1.5mg/dL or receiving dialysis).

• Female of childbearing potential (age <50 years and last menstruation within the last 12 months), who did not undergo tubal ligation, ovariectomy or hysterectomy.

• Life expectancy less than 1 year.

• Contraindication or known allergy against protocol-required medications including heparin, iodinated contrast, ß-blocker, nitroglycerin, and adenosine.

• Body mass index >35kg/m2.

• Complex congenital heart disease other than anomalous coronary origins alone.

• Ventricular septal defect.

Related Conditions & MeSH terms

• Constriction, Pathologic
• Coronary Stenosis

Intervention

Diagnostic Test:
• OCT, FFR, CTA and FFRCT
Multimodality assessment of intermediate left main stenosis: Comparison of optical coherence tomography-derived minimal lumen area, invasive fractional flow reserve and FFRCT

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire de Clermont-Ferrand	Clermont-Ferrand
France	Institute Mutualiste Montsouris	Paris
France	Centre Cardiologique du Nord	Saint-Denis
Germany	Friedrich Alexander Universität (FAU) , Medizinische Klinik 2 , Kardiologie und Angiologie	Erlangen
Germany	Universitätsklinikum Giessen Justus-Liebig Universität	Gießen	Hesse
Japan	Ageo Central General Hospital	Ageo
Japan	Gifu heart center	Gifu
Japan	Department of Cardiovascular Medicine Shinshu University School of Medicine	Nagano
Japan	Kansai Medical University,	Osaka
Japan	Medical Corporation Ouyuukai Tokorozawa Heart Center	Saitama
Japan	Sapporo Higashi Tokushukai Hospital	Sapporo
Switzerland	Inselspital	Bern
Switzerland	CHUV	Lausanne

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne

Countries where clinical trial is conducted

France,  Germany,  Japan,  Switzerland, 

References & Publications (5)

de la Torre Hernandez JM, Hernandez Hernandez F, Alfonso F, Rumoroso JR, Lopez-Palop R, Sadaba M, Carrillo P, Rondan J, Lozano I, Ruiz Nodar JM, Baz JA, Fernandez Nofrerias E, Pajin F, Garcia Camarero T, Gutierrez H; LITRO Study Group (Spanish Working Group on Interventional Cardiology). Prospective application of pre-defined intravascular ultrasound criteria for assessment of intermediate left main coronary artery lesions results from the multicenter LITRO study. J Am Coll Cardiol. 2011 Jul 19;58(4):351-8. doi: 10.1016/j.jacc.2011.02.064. — View Citation

Jasti V, Ivan E, Yalamanchili V, Wongpraparut N, Leesar MA. Correlations between fractional flow reserve and intravascular ultrasound in patients with an ambiguous left main coronary artery stenosis. Circulation. 2004 Nov 2;110(18):2831-6. doi: 10.1161/01.CIR.0000146338.62813.E7. Epub 2004 Oct 18. — View Citation

Makikallio T, Holm NR, Lindsay M, Spence MS, Erglis A, Menown IB, Trovik T, Eskola M, Romppanen H, Kellerth T, Ravkilde J, Jensen LO, Kalinauskas G, Linder RB, Pentikainen M, Hervold A, Banning A, Zaman A, Cotton J, Eriksen E, Margus S, Sorensen HT, Nielsen PH, Niemela M, Kervinen K, Lassen JF, Maeng M, Oldroyd K, Berg G, Walsh SJ, Hanratty CG, Kumsars I, Stradins P, Steigen TK, Frobert O, Graham AN, Endresen PC, Corbascio M, Kajander O, Trivedi U, Hartikainen J, Anttila V, Hildick-Smith D, Thuesen L, Christiansen EH; NOBLE study investigators. Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial. Lancet. 2016 Dec 3;388(10061):2743-2752. doi: 10.1016/S0140-6736(16)32052-9. Epub 2016 Oct 31. Erratum In: Lancet. 2016 Dec 3;388(10061):2742. — View Citation

Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ, Juni P, Kastrati A, Koller A, Kristensen SD, Niebauer J, Richter DJ, Seferovic PM, Sibbing D, Stefanini GG, Windecker S, Yadav R, Zembala MO; ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019 Jan 7;40(2):87-165. doi: 10.1093/eurheartj/ehy394. No abstract available. Erratum In: Eur Heart J. 2019 Oct 1;40(37):3096. — View Citation

Norgaard BL, Leipsic J, Gaur S, Seneviratne S, Ko BS, Ito H, Jensen JM, Mauri L, De Bruyne B, Bezerra H, Osawa K, Marwan M, Naber C, Erglis A, Park SJ, Christiansen EH, Kaltoft A, Lassen JF, Botker HE, Achenbach S; NXT Trial Study Group. Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). J Am Coll Cardiol. 2014 Apr 1;63(12):1145-1155. doi: 10.1016/j.jacc.2013.11.043. Epub 2014 Jan 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	OCT vs. FFR	- The area under the curve of OCT-derived MLA for FFR=0.8	Measurement at Procedure/ Baseline Visit
Primary	OCT vs. FFR	-The optimal cut-off point of OCT-derived MLA from receiver-operator characteristics curves for FFR=0.8	Measurement at Procedure/ Baseline Visit
Primary	FFRCT vs. FFR	Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FFRCT=0.8 for FFR=0.8	Measurement at Procedure/ Baseline Visit
Secondary	OCT vs. FFR, RFR, resting Pd/Pa, FFRCT, QFR	- The area under the curve and the optimal cut-off point of OCT-derived MLA from receiver-operator characteristics curves for FFR=0.75, RFR=0.89, resting Pd/Pa=0.91, and FFRCT=0.80 and QFR=0.80	Measurement at Procedure/ Baseline Visit
Secondary	OCT vs. FFR, RFR, resting Pd/Pa, FFRCT	- Predictability of MLA, minimal lumen diameter, area stenosis, lesion length, eccentricity index, and plaque characteristics (plaque rupture, fibroatheroma, and calcification) for FFR =0.8, FFR=0.75, RFR=0.89, resting Pd/Pa=0.91, and FFRCT=0.80 and QFR=0.80	Measurement at Procedure/ Baseline Visit
Secondary	OCT vs. FFR, RFR, resting Pd/Pa, FFRCT	- Correlation among OCT-derived MLA, FFR, RFR, resting Pd/Pa, and FFRCT and QFR	Measurement at Procedure/ Baseline Visit
Secondary	OCT vs. CTA	- Correlation between luminal diameter stenosis of CTA and OCT-derived MLA	Measurement at Procedure/ Baseline Visit
Secondary	OCT vs. CTA	- Diagnostic accuracy of plaque characteristics with presumed high risk characteristics including napkin ring sign, low attenuation plaque (<30HU), positive remodelling (remodelling index >1.1), and spotty calcium (<3mm) for thin and thick cap fibroatheroma by OCT.	Measurement at Procedure/ Baseline Visit
Secondary	Clinical endpoint at 1 year	Death	12 Month
Secondary	Clinical endpoint at 1 year	Myocardial infarction	12 Month
Secondary	Clinical endpoint at 1 year	Target vessel myocardial infarction	12 Month
Secondary	Clinical endpoint at 1 year	Target lesion revascularization	12 Month
Secondary	Clinical endpoint at 1 year	Target vessel revascularization	12 Month
Secondary	Clinical endpoint at 1 year	Any revascularization	12 Month
Secondary	Clinical endpoint at 1 year	Stent thrombosis	12 Month
Secondary	Clinical endpoint at 1 year	Stroke and transient ischemic attack	12 Month
Secondary	Clinical endpoint at 1 year	Acute renal failure	12 Month