Trial Evaluating New Strategy in the Functional Assessment of 3-vessel Disease Using SYNTAXII Score in Patients With PCI

Single-arm Trial Evaluating the Effectiveness of PCI of de Novo 3-vessel Disease Applying the SYNTAX Score II With Pressure Wire Functional Assessment and IVUS Guidance, Using an Everolimus-eluting Stent With Biodegradable Abluminal Coating

Clinical study that aims to evaluate a new strategy using the SYNTAX II Score calculator in the functional assessment of patients with new coronary 3-vessel-disease who undergo percutaneous coronary intervention (PCI)

Study Overview

• Status: Completed
• Conditions: Heart Diseases; Cardiovascular Diseases; 3 Vessel Coronary Artery Disease
• Intervention / Treatment: Device: Coronary stent; Radiation: Multi Slice Computed Tomography; Device: instantaneous wave-free ratio; Device: Fractional flow reserve; Device: Intravascular Ultrasound

Detailed Description

The purpose of the SYNTAX II Trial is to investigate the management of de-novo 3-vessel-disease in order to prospectively assess which patients would have at least comparable short and long term clinical outcomes between coronary artery bypass graft and percutaneous coronary intervention (PCI), using contemporary PCI practice. In SYNTAX II the effectiveness of a contemporary stent (designed with thinner struts, biocompatible and biodegradable polymer, and a limus based drug), the use of pressure wire assessment of lesions to allow for ischemia-driven revascularisation, intravascular ultrasound (IVUS) guidance to optimise drug eluting stent deployment, and the treatment of (chronic) total occlusion lesions with contemporary techniques, will be compared against PCI practice in the original SYNTAX trial. The proposed study would involve the SYNTAX Score II to prospectively recruit subjects on the grounds of patient safety

• Study Type: Observational
• Enrollment (Actual): 454

Contacts and Locations

Study Locations

• Netherlands
  • Noord Holland
    • Amsterdam, Noord Holland, Netherlands
      • Research Center NL007
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands
      • Research Center NL001
• Poland
  • Bielsko-Biała, Poland
    • Research Center PL008
  • Katowice, Poland
    • Research Center PL012
  • Krakow, Poland
    • Research Center PL010
  • Poznan, Poland
    • Research Center PL004
• Spain
  • Salamanca, Spain
    • Research Center ES016
  • Cantabria
    • Santander, Cantabria, Spain
      • Research Center ES009
  • Cataluna
    • Barcelona, Cataluna, Spain
      • Research Center ES001
  • Comunidad Autonoma De Madrid
    • Madrid, Comunidad Autonoma De Madrid, Spain
      • Research Center ES007
    • Madrid, Comunidad Autonoma De Madrid, Spain
      • Research Center ES012
    • Madrid, Comunidad Autonoma De Madrid, Spain
      • Research Center ES015
  • Galicia
    • Vigo, Galicia, Spain
      • Research Center ES004
• United Kingdom
  • Brighton, United Kingdom
    • Research Center GB005
  • Cambridge, United Kingdom
    • Research Center GB020
  • Edinburgh, United Kingdom
    • Research Center GB015
  • Liverpool, United Kingdom
    • Research Center GB001
  • London, United Kingdom
    • Research Center GB017
  • Manchester, United Kingdom
    • Research Center GB006
  • Newcastle upon Tyne, United Kingdom
    • Research Center GB013
  • County Antrim
    • Belfast, County Antrim, United Kingdom
      • Research Center GB014
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom
      • Research Center GB019

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with de novo 3 vessel disease

Description

Inclusion Criteria:

• At least 1 stenosis, angiographic, visually determined de novo lesions with more than 50 percent diameter stenosis in all 3 major epicardial territories. These are left descending coronary artery (LAD) and or side branch, proximal circumflex coronary artery (LCX) and or side branch, right descending coronary artery (RCA) and or side branch which are supplying viable myocardium without left main involvement. Patients with ostial LAD or ostial CX Medina 0,0,1 or Medina 0,1,0 may be enrolled
• Patients with hypoplastic RCA with absence of descending posterior and presence of a lesion in the LAD and CX territories may be included in the trial as a 3 vessel disease equivalent
• Vessel size should be at least 1.5 mm in diameter as visually assessed in diagnostic angiogram

• Patients with

  1. stable (Canadian Cardiovascular Society Class 1, 2, 3 or 4) angina pectoris
  2. or unstable (Braunwald class) angina pectoris and ischemia
  3. or patients with atypical chest pain or those who are asymptomatic provided they have myocardial ischemia, for example treadmill exercise test, radionuclide scintigraphy, stress echocardiography
• All anatomical SYNTAX Scores are eligible for initial screening with the SYNTAX Score II
• Patient has been informed of the nature of the study and agrees to its provisions and has provided written informed consent as approved by the Ethical Committee of the respective clinical site
• Signed Heart Team Decision Form between local cardiologist and surgeon that the selected case meets all of the inclusion and exclusion criteria

Exclusion Criteria:

• Under the age of 21 years
• Known pregnancy at time of enrolment. Female of childbearing potential, and last menstruation within the last 12 months, who are not taking adequate contraceptives. Female who is breastfeeding at time of enrolment
• Prior PCI or CABG
• Ongoing acute myocardial infarction and enzymes (CKMB) more than 2x upper limit of normal
• Concomitant cardiac valve disease requiring surgical therapy, reconstruction or replacement
• Single or two-vessel disease at time of Heart Team consensus
• Participation or planned participation in another cardiovascular clinical study before one year follow up is completed
• Mental condition, psychiatric or organ cerebral disease, rendering the subject unable to understand the nature, scope, and possible consequences of the study or mental retardation or language barrier such that the patient is unable to give informed consent and potential for non-compliance towards the requirement in the study protocol

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Percutaneous Coronary Intervention; All patients (single arm study) will be receiving the SYNERGY™ Everolimus eluting stent (EES)

Device: Coronary stent; Other Names: SYNERGY™ EES; Radiation: Multi Slice Computed Tomography; A coronary non-invasive Multi Slice Computed Tomography will be performed in patients; Other Names: MSCT; Device: instantaneous wave-free ratio; Pressure-derived, adenosine-free index on physiological assessment of stenosis severity; Other Names: iFR; Device: Fractional flow reserve; Pressure-derived index on physiological assessment of stenosis severity; Other Names: FFR; Device: Intravascular Ultrasound; Allows the application of ultrasound technology to see from inside blood vessels out through the surrounding blood column, visualizing the inner wall of blood vessels; Other Names: IVUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Umber of Participants With Major Adverse Cardiac and Cerebrovascular Events (MACCE)	MACCE is defined as: all-cause death; cerebrovascular event (stroke); documented myocardial infarction or all-cause revascularization	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With All-cause Death, Stroke, or Myocardial Infarction	Safety endpoint	1 Year
Number of Participants With All-cause Death	All-cause death	1 Year
Number of Participants With Stroke	Stroke	1 Year
Number of Participants With Myocardial Infarction	Any myocardial infarction	1 year
Number of Participants With Revascularization	Any coronary revascularization	1 Years
Number of Participants With Definite Stent Thrombosis	Stent Thrombosis - according to ARC definitions. Definite ST can be confirmed with 1) angiography (the presence of a thrombus that originates in the stent or in the segment 5 mm proximal or distal to the stent and presence of at least 1 of the following criteria within a 48-hour time window: Acute onset of ischemic symptoms at rest; New ischemic ECG changes that suggest acute ischemia; Typical rise and fall in cardiac biomarkers (refer to definition of spontaneous MI); Non-occlusive thrombus or Occlusive thrombus; or 2) Pathological confirmation (evidence of recent thrombus within the stent determined at autopsy or via examination of tissue retrieved following thrombectomy).	1 Year
Number of Participants With Probable Stent Thrombosis	Stent Thrombosis - according to ARC definitions. Clinical definition of probable stent thrombosis is considered to have occurred after intracoronary stenting in the following cases: 1) Any unexplained death within the first 30 days; 2) Irrespective of the time after the index procedure, any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause.	1 year

Collaborators and Investigators

• Sponsor: ECRI bv
• Collaborators: Boston Scientific Corporation; Volcano Corporation
• Investigators: Principal Investigator: Javier Escaned, MD, Hospital San Carlos Madrid, Spain; Principal Investigator: Adrian Banning, MD, John Radcliffe Hospital, Oxford, United Kingdom

Publications and helpful links

General Publications

• Wang R, Kawashima H, Hara H, Gao C, Ono M, Takahashi K, Tu S, Soliman O, Garg S, van Geuns RJ, Tao L, Wijns W, Onuma Y, Serruys PW. Comparison of Clinically Adjudicated Versus Flow-Based Adjudication of Revascularization Events in Randomized Controlled Trials. Circ Cardiovasc Qual Outcomes. 2021 Nov;14(11):e008055. doi: 10.1161/CIRCOUTCOMES.121.008055. Epub 2021 Oct 20.
• Collet C, Miyazaki Y, Ryan N, Asano T, Tenekecioglu E, Sonck J, Andreini D, Sabate M, Brugaletta S, Stables RH, Bartorelli A, de Winter RJ, Katagiri Y, Chichareon P, De Maria GL, Suwannasom P, Cavalcante R, Jonker H, Morel MA, Cosyns B, Kappetein AP, Taggart DT, Farooq V, Escaned J, Banning A, Onuma Y, Serruys PW. Fractional Flow Reserve Derived From Computed Tomographic Angiography in Patients With Multivessel CAD. J Am Coll Cardiol. 2018 Jun 19;71(24):2756-2769. doi: 10.1016/j.jacc.2018.02.053. Epub 2018 May 22.
• Escaned J, Collet C, Ryan N, De Maria GL, Walsh S, Sabate M, Davies J, Lesiak M, Moreno R, Cruz-Gonzalez I, Hoole SP, Ej West N, Piek JJ, Zaman A, Fath-Ordoubadi F, Stables RH, Appleby C, van Mieghem N, van Geuns RJ, Uren N, Zueco J, Buszman P, Iniguez A, Goicolea J, Hildick-Smith D, Ochala A, Dudek D, Hanratty C, Cavalcante R, Kappetein AP, Taggart DP, van Es GA, Morel MA, de Vries T, Onuma Y, Farooq V, Serruys PW, Banning AP. Clinical outcomes of state-of-the-art percutaneous coronary revascularization in patients with de novo three vessel disease: 1-year results of the SYNTAX II study. Eur Heart J. 2017 Nov 7;38(42):3124-3134. doi: 10.1093/eurheartj/ehx512. Erratum In: Eur Heart J. 2018 May 7;39(18):1619.
• Farooq V, Serruys PW. Bypass Grafting Versus Percutaneous Intervention-Which Is Better in Multivessel Coronary Disease: Lessons From SYNTAX and Beyond. Prog Cardiovasc Dis. 2015 Nov-Dec;58(3):316-34. doi: 10.1016/j.pcad.2015.10.002. Epub 2015 Oct 31.

Helpful Links

• 5-year final results of the SYNTAX II trial

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 6, 2014
• Primary Completion (ACTUAL): March 28, 2017
• Study Completion (ACTUAL): February 4, 2021

Study Registration Dates

• First Submitted: December 13, 2013
• First Submitted That Met QC Criteria: December 13, 2013
• First Posted (ESTIMATE): December 19, 2013

Study Record Updates

• Last Update Posted (ACTUAL): July 21, 2022
• Last Update Submitted That Met QC Criteria: July 12, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Stents; Angioplasty; Drug eluting stents; intravascular ultrasound; fractional flow reserve; SYNTAX II Score; Pressure wires; instantaneous wave-free ratio; multi slice computed tomography
• Additional Relevant MeSH Terms: Myocardial Ischemia; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Diseases; Coronary Artery Disease; Cardiovascular Diseases
• Other Study ID Numbers: ECRI-002