Clinical trial NCT02813473: SYNTAX III REVOLUTION Trial: A Randomized Study Investigating the Use of CT Scan and Angiography of the Heart to Help the Doctors Decide Which Method is the Best to Improve Blood Supply to the Heart in Patients With Complex Coronary Artery Disease
Official title: SYNTAX III REVOLUTION Trial: A Randomized Study to Evaluate the Feasibility of Heart-Team Clinical Decision Making Regarding the Optimal (Surgical or Percutaneous Based) Revascularization Strategy in Patients With Complex Coronary Artery Disease, Based on Non-invasive Coronary CT Angiography (CTA) Imaging Utilising High-definition GE RevolutionTM Multi-slice CT and HeartFlow FFRCT Compared to the Current Standard of Care With Conventional Invasive Coronary Angiography (CA)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Diseases
Multivessel Coronary Artery Disease
Heart Diseases
Cardiovascular Diseases
Keywords: SYNTAX Score II
Multi Slice Computed Tomography
MSCT
Heart Team
Fractional Flow Reserve Computed Tomography
FFR
FFR MSCT
PCI
CABG
Percutaneous Coronary Intervention
Coronary Artery Bypass Graft
Lead sponsor: ECRI bv
Sponsor class: INDUSTRY
Collaborators: name: GE Healthcare
name: HeartFlow, Inc.
First posted: 2016-06-27
Enrollment: 223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with complex coronary artery disease, defined as: left main (isolated, or associated with 1, 2 or 3 vessel disease) or de novo 3-vessel coronary artery disease (DS ≥50%), who are able to undergo cardiac CT with a GE high-definition RevolutionTM multi-slice CT scanner.

Brief summary: The SYNTAX III Revolution trial is a randomized diagnostic research study that investigates the use of CT scan and angiogram of the heart to help doctors decide which method is the best to improve blood supply to the heart in patients with complex coronary artery disease. Each patient will undergo an angiogram and CT scan per standard of care. The randomization strategy in this study is not between patients but between two teams of doctors, the so-called "Heart Teams", will be randomized: in the first round, team 1 assesses the angiogram, and team 2 assesses the CT scan. Then they make a decision about which treatment would be the best to treat complex coronary artery disease. In the second round, both teams see the imaging method that they did not see in the first round, and make the decision again. The final decision on the clinical treatment strategy is at the sole discretion of the Heart Team and there are no criteria described in SYNTAXIII Revolution protocol leading influencing this final decision.

Hypothesis: Determination of the best treatment strategy for coronary artery disease based on a CT scan will result in similar decisions as based on invasive coronary angiography.

Detailed description: The SYNTAX III REVOLUTION Trial is a multicenter, all-comers trial (either isolated unprotected left-main or 3-vessel disease with or without left-main disease and candidate for either CABG or PCI treatment). In SYNTAXIII REVOLUTION a diagnostic coronary angiography and a diagnostic coronary Multislice CT are performed to allow the Heart Team to assess the optimal revascularization strategy. In a normal hospital setting the angiography is considered standard of care. The multislice CT can already also be part of the diagnosis and is at the discretion of the physician. After the images of both modalities are available, the patient will no longer participate in the trial. Next step is randomization of Heart Team A and Heart B to the sequence of availability of images, i.e. randomizing whether Heart Team A will review the angiography first or the multislice CT and, automatically, Heart B the other modality. The Heart Teams need to make a decision between surgical or percutaneous treatment according to either the conventional angiography or the multislice CT angiography assessment. In addition, the incremental value of FFRCT in the decision making of the Heart Team arm allocated primarily to the assessment of the MSCT (CT first algorithm) will be a secondary endpoint. No intervention to the patient's treatment takes place

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Eligibility criteria: Inclusion Criteria:

1. Patients with at least 1 stenosis (angiographic, visually determined de novo lesions with ≥50% DS) in all 3 major epicardial territories (LAD and/or side branch, CX and/or side branch, RCA and/or side branch) supplying viable myocardium with or without left main involvement;
2. 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 3VD equivalent;
3. Vessel size should be at least 1.5 mm in diameter as visually assessed in diagnostic angiogram;
4. Patients with chronic stable angina or stabilized acute coronary syndrome (inclusion criteria of the SYNTAX I study):

   * stable (Canadian Cardiovascular Society Class 1, 2, 3 or 4) angina pectoris;
   * or unstable (Braunwald class IB, IC, IIB, IIC, IIIB, IIIC) angina pectoris and ischemia with normal cardiac enzyme values prior to enrollment;
   * or patients with atypical chest pain or those who are asymptomatic provided they have myocardial ischemia (e.g. treadmill exercise test, radionuclide scintigraphy, stress echocardiography);
5. All anatomical SYNTAX Scores are eligible;
6. Patient amenable to a MSCT coronary angiography (e.g. no claustrophobia, high heartrate not amenable to beta-blockers, poor renal function, etc., up to discretion of investigator);
7. 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;

Exclusion Criteria:

1. Under the age of 18 years;
2. Unable to give Informed Consent;
3. 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;
4. Prior PCI or CABG; history of coronary stent implantation;
5. Evidence of evolving or ongoing acute myocardial infarction (AMI) in ECG and/or elevated cardiac biomarkers (according to local standard hospital practice) have not returned within normal limits at the time of enrollment;
6. Concomitant cardiac valve disease requiring surgical therapy (reconstruction or replacement);
7. Single or two-vessel disease (at time of Heart Team consensus);
8. Atrial fibrillation or significant arrhythmias;
9. Known allergy to iodinated contrast;
10. A Body Mass Index (BMI) of 35 or greater;
11. Participation in another trial with an investigational drug or device.

Primary outcomes:
measure: Inter-rater Agreement on Revascularization Strategy of Two Heart Teams Using an "Angio-first" Algorithm or a "CT First" Algorithm.
timeFrame: Heart Team meetings took place in average 1 to 2 weeks afer patient enrollment
Secondary outcomes:
measure: Level of Agreement in the Decision Making Strategy Based on CT Only Without Functional Assessment and the Decision Making Strategy Based on CT With Functional Assessment ("CT First" Algorithm Group) at Screening.
timeFrame: Nov 2017
measure: Level of Agreement in the Decision Making Strategy Based on CT Only (With Functional Assessment) and the Decision Making Strategy Based on CT With Functional Assessment and Conventional Angiography ("CT First" Algorithm Group) at Screening
timeFrame: Nov 2017
measure: Level of Agreement in the Decision Making Strategy Based on Conventional Angiography Only and the Decision Making Strategy Based on CT With Functional Assessment and Conventional Angiography ("Angio First" Algorithm Group) at Screening
timeFrame: Nov 2017
measure: Inter-rater Agreement on Revascularization Strategy (Based on Conventional Angiography and CT With Functional Assessment) of Two Heart Teams Using an "Angio-first" Algorithm or a "CT-first" Algorithm at Screening
timeFrame: Nov 2017
measure: Anatomical SYNTAX Score Calculation Based on Non-invasive GE Revolution CT (Visual by Heart Team Involving an Experienced Coronary CT Reader) and the Resulting SYNTAX Score II at Screening
timeFrame: Nov 2017
measure: Anatomical SYNTAX Score Calculation Based on Non-invasive GE Revolution CT (Visual by Core Lab) and the Resulting SYNTAX Score II at Screening
timeFrame: Nov 2017
measure: Anatomical SYNTAX Score Calculation Based Invasive Angiography (Visual by Heart Team) and the Resulting SYNTAX Score II at Screening
timeFrame: Nov 2017
measure: Anatomical SYNTAX Score Calculation Based on Invasive Angiography (Visual by Core Lab) and the Resulting SYNTAX Score II at Screening
timeFrame: Nov 2017
measure: CT Based Functional Anatomy (FFRCT as Assessed by Heartflow) at Screening
timeFrame: Nov 2017
measure: Concordance in SYNTAX Score(s) Between and Within Strategies at Screening
timeFrame: Nov 2017
measure: Agreement in Coronary Stenosis Segments to be Revascularized Between and Within Strategies at Screening
timeFrame: Nov 2017
Other outcomes:
Locations:
city: Brussel
country: Belgium
facility: BE006
city: Nancy
country: France
facility: FR013
city: Paris
country: France
facility: FR012
city: Jena
country: Germany
facility: DE011
city: Milan
country: Italy
facility: IT008
city: Zurich
country: Switzerland
facility: CH003
Study officials:
affiliation: Imperial College, London (UK)
name: Patrick W Serruys, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Andreini D, Modolo R, Katagiri Y, Mushtaq S, Sonck J, Collet C, De Martini S, Roberto M, Tanaka K, Miyazaki Y, Czapla J, Schoors D, Plass A, Maisano F, Kaufmann P, Orry X, Metzdorf PA, Folliguet T, Farber G, Diamantis I, Schonweiss M, Bonalumi G, Guglielmo M, Ferrari C, Olivares P, Cavallotti L, Leal I, Lindeboom W, Onuma Y, Serruys PW, Bartorelli AL; SYNTAX III REVOLUTION Investigators. Impact of Fractional Flow Reserve Derived From Coronary Computed Tomography Angiography on Heart Team Treatment Decision-Making in Patients With Multivessel Coronary Artery Disease: Insights From the SYNTAX III REVOLUTION Trial. Circ Cardiovasc Interv. 2019 Dec;12(12):e007607. doi: 10.1161/CIRCINTERVENTIONS.118.007607. Epub 2019 Dec 13.
citation: Collet C, Onuma Y, Andreini D, Sonck J, Pompilio G, Mushtaq S, La Meir M, Miyazaki Y, de Mey J, Gaemperli O, Ouda A, Maureira JP, Mandry D, Camenzind E, Macron L, Doenst T, Teichgraber U, Sigusch H, Asano T, Katagiri Y, Morel MA, Lindeboom W, Pontone G, Luscher TF, Bartorelli AL, Serruys PW. Coronary computed tomography angiography for heart team decision-making in multivessel coronary artery disease. Eur Heart J. 2018 Nov 1;39(41):3689-3698. doi: 10.1093/eurheartj/ehy581.