Coronary Artery Disease
Conditions
Keywords
Three-vessel coronary artery disease, Left main coronary artery disease
Brief summary
The SYNTAX trial is designed to determine the best treatment for patients with complex coronary disease (blocked or narrowed arteries in both the right and left sides of the heart) by randomizing patients to receive either percutaneous coronary intervention (PCI) with polymer-based paclitaxel-eluting TAXUS stents or to coronary artery bypass surgery (CABG).
Detailed description
Due to the introduction of drug-eluting stents (DESs) and to improvements in therapy for both percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG) patients, PCI is challenging CABG as the gold standard for treatment of three vessel (3VD) and left main (LM) coronary disease. SYNTAX is a novel, randomized trial with nested registries comparing PCI with paclitaxel-eluting TAXUS stents to CABG for 3VD and LM patients to evaluate the best treatment for these patients with complex coronary disease. Patients at participating centers will be evaluated by both a cardiothoracic surgeon and by an interventional cardiologist. Those patients who are determined to be eligible for treatment by both PCI and CABG will be randomized to receive either PCI with a polymer-based paclitaxel-eluting TAXUS stent or CABG. Patients who are determined to be unsuitable for treatment by PCI will be treated by CABG and will be entered into a CABG registry to help define the patient population in which stenting continues to be an unacceptable treatment option. Similarly, patients who are determined to be unsuitable for treatment by CABG will be treated by PCI, using any interventional techniques or devices with or without the use of DES, and entered into a PCI registry to help define the patients for whom CABG is considered inappropriate.
Interventions
DEVICEPolymer-based Paclitaxel-Eluting TAXUS Express2-SR Stent
Drug Eluting Stent
PROCEDURECoronary Artery Bypass Surgery
Coronary Artery Bypass Surgery
Sponsors
Cardialysis BV
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Three-vessel disease, left main disease or LM equivalent with or without 1, 2 or 3VD (left anterior descending \[LAD\], left circumflex \[LCX\], right coronary artery \[RCA\] territory) * De novo lesions with at least 50% stenosis * Myocardial ischemia (stable, unstable, silent)
Exclusion criteria
* Prior PCI or CABG * Acute myocardial infarction (with creatinine kinase \>2x upper limit of normal) * Concomitant cardiac valve disease requiring surgical therapy (reconstruction or replacement) * Participation or planned participation in another cardiovascular clinical study before 1 year follow-up is completed * Inability to give informed consent due to mental condition, mental retardation, or language barrier
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Repeat Revascularization (PCI and/or CABG). | 12 Months post enrollment | Number of participants with repeat revascularization (PCI and/or CABG). |
| Primary Clinical Endpoint of 12-Month Binary MACCE. | 12 months post enrollment | Number of participants at primary clinical endpoint of 12-Month binary MACCE. MACCE is defined as: all cause death, cerebrovascular event (stroke), cocumented myocardial infarction, repeat revascularization (PCI and/or CABG). |
| 12-month Composite Safety Endpoint. | 12 months after enrollment | Number of participants at 12-month composite safety endpoint. Composite safety endpoint combines: all cause death, cerebrovascular event (stroke), and documented myocardial infarction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Individual Components of MACCE at 1 Year Post-allocation. | 1 year post allocation | Number of participants with individual components of MACCE at 1 year post-allocation. The individual components of MACCE are: all cause death, stroke, documented myocardial infarction, repeat revascularization. |
| Freedom From MACCE and Its Components at 1 Year Post-allocation. | 1 year post allocation | Number of participants with freedom from MACCE and its components at 1 year post-allocation. Freedom from MACCE is defined as no MACCE nor any of the individual components of MACCE (all cause death, stroke, documented myocardial infarction, repeat revascularization). |
| Freedom From MACCE and Its Components at 3 Years Post-allocation | 3 years post allocation | — |
| Overall MACCE at 1 Month Post-procedure and at 6 Months, 3 Years, and 5 Years Post-allocation. | 1 month after procedure and 6 months, 3 years, and 5 years post allocation | Number of participants with Overall MACCE at 1 month post-procedure and at 6 months, 3 years, and 5 years post-allocation. |
| Quality of Life at 1 Month Post-procedure and at 6 Months, 1, 3 and 5 Years Post-allocation | 1 month after procedure and 6 months, 1, 3 and 5 years post allocation | — |
| Cost and Cost-effectiveness at 1, 3 and 5 Years Post-allocation | 1 year, 3 and 5 years post allocation | — |
| The Characteristics (Including Co-morbidity and Coronary Vascular Lesion Complexity Scoring Referred to as the SYNTAX Score) of the Following: PCI Versus CABG Randomized Cohort, PCI Registry Cohort (CABG Ineligible), CABG Registry Cohort (PCI Ineligible) | 5 Years | — |
| Freedom From MACCE and Its Components at 5 Years Post-allocation | 5 years post allocation | — |
| Individual Components of MACCE at 1 Month Post-procedure. | 1 month after procedure | Number of participants with individual components of MACCE at 1 month post-procedure. The individual components of MACCE are: all cause death, stroke, documented myocardial infarction, repeat revascularization. |
| Individual Components of MACCE at 6 Months Post-allocation. | 6 months post allocation | Number of participants with individual components of MACCE at 6 months post-allocation. The individual components of MACCE are: all cause death, stroke, documented myocardial infarction, repeat revascularization. |
Countries
Austria, Belgium, Czechia, Denmark, Finland, France, Germany, Hungary, Italy, Latvia, Netherlands, Norway, Poland, Portugal, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CABG Coronary Artery By-pass Graft (CABG) | 897 |
| PCI With DES Percutaneous coronary intervention (PCI) using TAXUS Express Drug Eluting Stent (DES) | 903 |
| Total | 1,800 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 8 | 5 |
| Overall Study | Withdrawal by Subject | 40 | 7 |
Baseline characteristics
| Characteristic | Total | CABG | PCI With DES |
|---|---|---|---|
| Additive Euroscore | 3.77 units on a scale STANDARD_DEVIATION 2.66 | 3.79 units on a scale STANDARD_DEVIATION 2.69 | 3.75 units on a scale STANDARD_DEVIATION 2.62 |
| Age, Categorical <=18 years | 0.0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1003.0 Participants | 497 Participants | 506 Participants |
| Age, Categorical Between 18 and 65 years | 797.0 Participants | 400 Participants | 397 Participants |
| Age Continuous | 65.09 years STANDARD_DEVIATION 9.72 | 64.96 years STANDARD_DEVIATION 9.79 | 65.23 years STANDARD_DEVIATION 9.66 |
| Angina Participants with No Angina at Baseline | 113.0 participants | 59 participants | 54 participants |
| Angina Participants with Silent Ischemia at Baseline | 148.0 participants | 74 participants | 74 participants |
| Angina Participants with Stable Angina at Baseline | 1027.0 participants | 513 participants | 514 participants |
| Angina Participants with Unstable Angina at Baseline | 512.0 participants | 251 participants | 261 participants |
| Bifurcation lesion (per participant) No Bifurcated Lesions | 499.0 participants | 245 participants | 254 participants |
| Bifurcation lesion (per participant) One or more Bifurcated Lesion(s) | 1301.0 participants | 652 participants | 649 participants |
| Blood pressure ≥130/85 mmHg Blood Pressure <130/85 mmHG | 604.0 participants | 323 participants | 281 participants |
| Blood pressure ≥130/85 mmHg Blood Pressure >= 130/85 mmHG | 1196.0 participants | 574 participants | 622 participants |
| Body Mass Index (BMI) | 28.01 kg/m2 STANDARD_DEVIATION 4.67 | 27.91 kg/m2 STANDARD_DEVIATION 4.54 | 28.11 kg/m2 STANDARD_DEVIATION 4.8 |
| Carotid artery disease Diagnosed Carotid Artery Disease at Baseline | 148.0 participants | 75 participants | 73 participants |
| Carotid artery disease No Diagnosed Carotid Artery Disease at Baseline | 1652.0 participants | 822 participants | 830 participants |
| Congestive heart failure Congestive Heart Failure at Baseline | 83.0 participants | 47 participants | 36 participants |
| Congestive heart failure No Congestive Heart Failure at Baseline | 1717.0 participants | 850 participants | 867 participants |
| Current smoking Non-Smokers at Baseline | 1437.0 participants | 701 participants | 736 participants |
| Current smoking Smokers at Baseline | 363.0 participants | 196 participants | 167 participants |
| Diabetes Diagnosed Diabetes at Baseline | 511.0 participants | 256 participants | 255 participants |
| Diabetes No Diagnosed Diabetes at Baseline | 1289.0 participants | 641 participants | 648 participants |
| HDL cholesterol (<40 Male or <50 Female) Participant HDL Greater Than Limit at Baseline | 1017.0 participants | 493 participants | 524 participants |
| HDL cholesterol (<40 Male or <50 Female) Participant HDL Less Than Limit at Baseline | 783.0 participants | 404 participants | 379 participants |
| Hyperlipidemia Participants with Hyperlipidemia at Baseline | 1391.0 participants | 686 participants | 705 participants |
| Hyperlipidemia Participants without Hyperlipidemia at Baseline | 409.0 participants | 211 participants | 198 participants |
| Insulin requiring diabetes Nondiabetic Participants | 1289.0 participants | 641 participants | 648 participants |
| Insulin requiring diabetes Participants with Insulin dependent Diabetes | 182.0 participants | 93 participants | 89 participants |
| Insulin requiring diabetes Participants with non-Insulin independent Diabetes | 329.0 participants | 163 participants | 166 participants |
| Medically treated Diabetes Diabetic Participants Medically Treated | 452.0 Participants | 221 Participants | 231 Participants |
| Medically treated Diabetes Diabetic Participants Treated through Diet only | 59.0 Participants | 35 Participants | 24 Participants |
| Medically treated Diabetes Non-Diabetic Participants | 1289.0 Participants | 641 Participants | 648 Participants |
| Metabolic Syndrome Participants with a Metabolic Syndrome | 656.0 participants | 317 participants | 339 participants |
| Metabolic Syndrome Participants without a Metabolic Syndrome | 1144.0 participants | 580 participants | 564 participants |
| Number of lesions per partipant | 3.97 Number of lesions/Participant STANDARD_DEVIATION 1.68 | 3.99 Number of lesions/Participant STANDARD_DEVIATION 1.7 | 3.94 Number of lesions/Participant STANDARD_DEVIATION 1.66 |
| Parsonnet Score | 8.48 units on a scale STANDARD_DEVIATION 6.9 | 8.43 units on a scale STANDARD_DEVIATION 6.84 | 8.53 units on a scale STANDARD_DEVIATION 6.95 |
| Poor LVEF LVEF <30% at Baseline | 34.0 participants | 22 participants | 12 participants |
| Poor LVEF LVEF >=30% at Baseline | 1766.0 participants | 875 participants | 891 participants |
| Prior MI Myocardial Infarction Before Baseline | 585.0 participants | 300 participants | 285 participants |
| Prior MI No Myocardial Infarction Before Baseline | 1215.0 participants | 597 participants | 618 participants |
| Prior Stroke No Stroke Prior to Baseline | 1722.0 participants | 854 participants | 868 participants |
| Prior Stroke Stroke Prior to Baseline | 78.0 participants | 43 participants | 35 participants |
| Prior TIA No Transient Ischemic Attack before baseline | 1716.0 participants | 852 participants | 864 participants |
| Prior TIA Transient Ischemic Attack Before Baseline | 84.0 participants | 45 participants | 39 participants |
| Region of Enrollment Austria | 52.0 participants | 24 participants | 28 participants |
| Region of Enrollment Belgium | 91.0 participants | 47 participants | 44 participants |
| Region of Enrollment Czech Republic | 40.0 participants | 20 participants | 20 participants |
| Region of Enrollment Denmark | 32.0 participants | 15 participants | 17 participants |
| Region of Enrollment Finland | 24.0 participants | 12 participants | 12 participants |
| Region of Enrollment France | 208.0 participants | 105 participants | 103 participants |
| Region of Enrollment Germany | 179.0 participants | 93 participants | 86 participants |
| Region of Enrollment Hungary | 83.0 participants | 39 participants | 44 participants |
| Region of Enrollment Italy | 197.0 participants | 96 participants | 101 participants |
| Region of Enrollment Latvia | 40.0 participants | 20 participants | 20 participants |
| Region of Enrollment Netherlands | 148.0 participants | 74 participants | 74 participants |
| Region of Enrollment Norway | 8.0 participants | 4 participants | 4 participants |
| Region of Enrollment Poland | 66.0 participants | 33 participants | 33 participants |
| Region of Enrollment Portugal | 13.0 participants | 7 participants | 6 participants |
| Region of Enrollment Spain | 53.0 participants | 26 participants | 27 participants |
| Region of Enrollment Sweden | 54.0 participants | 28 participants | 26 participants |
| Region of Enrollment United Kingdom | 267.0 participants | 132 participants | 135 participants |
| Region of Enrollment United States | 245.0 participants | 122 participants | 123 participants |
| Sex: Female, Male Female | 402 Participants | 189 Participants | 213 Participants |
| Sex: Female, Male Male | 1398 Participants | 708 Participants | 690 Participants |
| Total Occlusion (per patient) Participants with at least One Total Occlusion | 415.0 participants | 198 participants | 217 participants |
| Total Occlusion (per patient) Participants with Partial Occlusion(s) | 1385.0 participants | 699 participants | 686 participants |
| Total Syntax Score | 28.7 units on a scale STANDARD_DEVIATION 11.42 | 29.1 units on a scale STANDARD_DEVIATION 11.37 | 28.39 units on a scale STANDARD_DEVIATION 11.46 |
| Triglyceride levels ≥150 mg/dL Participants with Triglyceride Levels <150 mg/dL | 1221.0 participants | 593 participants | 628 participants |
| Triglyceride levels ≥150 mg/dL Participants with Triglyceride Levels >= 150 mg/dL | 579.0 participants | 304 participants | 275 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 509 / 897 | 405 / 903 |
| serious Total, serious adverse events | 391 / 897 | 357 / 903 |
Outcome results
Primary
12-month Composite Safety Endpoint.
Number of participants at 12-month composite safety endpoint. Composite safety endpoint combines: all cause death, cerebrovascular event (stroke), and documented myocardial infarction.
Time frame: 12 months after enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CABG | 12-month Composite Safety Endpoint. | 65 participants |
| PCI With DES | 12-month Composite Safety Endpoint. | 68 participants |
Primary
Primary Clinical Endpoint of 12-Month Binary MACCE.
Number of participants at primary clinical endpoint of 12-Month binary MACCE. MACCE is defined as: all cause death, cerebrovascular event (stroke), cocumented myocardial infarction, repeat revascularization (PCI and/or CABG).
Time frame: 12 months post enrollment
Population: ITT analysis. Number of participants analyzed equals number of subjects who completed Overall Study, as listed in Participant Flow.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CABG | Primary Clinical Endpoint of 12-Month Binary MACCE. | 105 participants |
| PCI With DES | Primary Clinical Endpoint of 12-Month Binary MACCE. | 159 participants |
Primary
Repeat Revascularization (PCI and/or CABG).
Number of participants with repeat revascularization (PCI and/or CABG).
Time frame: 12 Months post enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CABG | Repeat Revascularization (PCI and/or CABG). | 50 Participants |
| PCI With DES | Repeat Revascularization (PCI and/or CABG). | 120 Participants |
Secondary
Cost and Cost-effectiveness at 1, 3 and 5 Years Post-allocation
Time frame: 1 year, 3 and 5 years post allocation
Secondary
Freedom From MACCE and Its Components at 1 Year Post-allocation.
Number of participants with freedom from MACCE and its components at 1 year post-allocation. Freedom from MACCE is defined as no MACCE nor any of the individual components of MACCE (all cause death, stroke, documented myocardial infarction, repeat revascularization).
Time frame: 1 year post allocation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CABG | Freedom From MACCE and Its Components at 1 Year Post-allocation. | Freedom from any cause death | 819 participants |
| CABG | Freedom From MACCE and Its Components at 1 Year Post-allocation. | Freedom from documented MI | 821 participants |
| CABG | Freedom From MACCE and Its Components at 1 Year Post-allocation. | Freedom from stroke | 830 participants |
| CABG | Freedom From MACCE and Its Components at 1 Year Post-allocation. | Freedom from any repeat revascularization | 799 participants |
| CABG | Freedom From MACCE and Its Components at 1 Year Post-allocation. | Freedom from any MACCE | 744 participants |
| PCI With DES | Freedom From MACCE and Its Components at 1 Year Post-allocation. | Freedom from any repeat revascularization | 771 participants |
| PCI With DES | Freedom From MACCE and Its Components at 1 Year Post-allocation. | Freedom from any MACCE | 732 participants |
| PCI With DES | Freedom From MACCE and Its Components at 1 Year Post-allocation. | Freedom from any cause death | 852 participants |
| PCI With DES | Freedom From MACCE and Its Components at 1 Year Post-allocation. | Freedom from stroke | 886 participants |
| PCI With DES | Freedom From MACCE and Its Components at 1 Year Post-allocation. | Freedom from documented MI | 848 participants |
Secondary
Freedom From MACCE and Its Components at 3 Years Post-allocation
Time frame: 3 years post allocation
Secondary
Freedom From MACCE and Its Components at 5 Years Post-allocation
Time frame: 5 years post allocation
Secondary
Individual Components of MACCE at 1 Month Post-procedure.
Number of participants with individual components of MACCE at 1 month post-procedure. The individual components of MACCE are: all cause death, stroke, documented myocardial infarction, repeat revascularization.
Time frame: 1 month after procedure
Population: ITT analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CABG | Individual Components of MACCE at 1 Month Post-procedure. | All cause death | 10 participants |
| CABG | Individual Components of MACCE at 1 Month Post-procedure. | Documented MI | 21 participants |
| CABG | Individual Components of MACCE at 1 Month Post-procedure. | Any repeat revascularization | 15 participants |
| CABG | Individual Components of MACCE at 1 Month Post-procedure. | Stroke | 9 participants |
| PCI With DES | Individual Components of MACCE at 1 Month Post-procedure. | Any repeat revascularization | 31 participants |
| PCI With DES | Individual Components of MACCE at 1 Month Post-procedure. | All cause death | 20 participants |
| PCI With DES | Individual Components of MACCE at 1 Month Post-procedure. | Stroke | 2 participants |
| PCI With DES | Individual Components of MACCE at 1 Month Post-procedure. | Documented MI | 31 participants |
Secondary
Individual Components of MACCE at 1 Year Post-allocation.
Number of participants with individual components of MACCE at 1 year post-allocation. The individual components of MACCE are: all cause death, stroke, documented myocardial infarction, repeat revascularization.
Time frame: 1 year post allocation
Population: ITT analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CABG | Individual Components of MACCE at 1 Year Post-allocation. | Death any cause | 30 participants |
| CABG | Individual Components of MACCE at 1 Year Post-allocation. | Stroke | 19 participants |
| CABG | Individual Components of MACCE at 1 Year Post-allocation. | Documented MI | 28 participants |
| CABG | Individual Components of MACCE at 1 Year Post-allocation. | Any repeat revascularization | 50 participants |
| PCI With DES | Individual Components of MACCE at 1 Year Post-allocation. | Any repeat revascularization | 120 participants |
| PCI With DES | Individual Components of MACCE at 1 Year Post-allocation. | Death any cause | 39 participants |
| PCI With DES | Individual Components of MACCE at 1 Year Post-allocation. | Documented MI | 43 participants |
| PCI With DES | Individual Components of MACCE at 1 Year Post-allocation. | Stroke | 5 participants |
Secondary
Individual Components of MACCE at 6 Months Post-allocation.
Number of participants with individual components of MACCE at 6 months post-allocation. The individual components of MACCE are: all cause death, stroke, documented myocardial infarction, repeat revascularization.
Time frame: 6 months post allocation
Population: ITT analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CABG | Individual Components of MACCE at 6 Months Post-allocation. | All cause death | 24 Participants |
| CABG | Individual Components of MACCE at 6 Months Post-allocation. | Stroke | 13 Participants |
| CABG | Individual Components of MACCE at 6 Months Post-allocation. | Documented MI | 27 Participants |
| CABG | Individual Components of MACCE at 6 Months Post-allocation. | Any repeat revascularization | 35 Participants |
| PCI With DES | Individual Components of MACCE at 6 Months Post-allocation. | Any repeat revascularization | 78 Participants |
| PCI With DES | Individual Components of MACCE at 6 Months Post-allocation. | All cause death | 31 Participants |
| PCI With DES | Individual Components of MACCE at 6 Months Post-allocation. | Documented MI | 40 Participants |
| PCI With DES | Individual Components of MACCE at 6 Months Post-allocation. | Stroke | 2 Participants |
Secondary
Overall MACCE at 1 Month Post-procedure and at 6 Months, 3 Years, and 5 Years Post-allocation.
Number of participants with Overall MACCE at 1 month post-procedure and at 6 months, 3 years, and 5 years post-allocation.
Time frame: 1 month after procedure and 6 months, 3 years, and 5 years post allocation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CABG | Overall MACCE at 1 Month Post-procedure and at 6 Months, 3 Years, and 5 Years Post-allocation. | MACCE 1 month post procedure | 45 participants |
| CABG | Overall MACCE at 1 Month Post-procedure and at 6 Months, 3 Years, and 5 Years Post-allocation. | MACCE 6 months post procedure | 85 participants |
| PCI With DES | Overall MACCE at 1 Month Post-procedure and at 6 Months, 3 Years, and 5 Years Post-allocation. | MACCE 1 month post procedure | 54 participants |
| PCI With DES | Overall MACCE at 1 Month Post-procedure and at 6 Months, 3 Years, and 5 Years Post-allocation. | MACCE 6 months post procedure | 111 participants |
Secondary
Quality of Life at 1 Month Post-procedure and at 6 Months, 1, 3 and 5 Years Post-allocation
Time frame: 1 month after procedure and 6 months, 1, 3 and 5 years post allocation
Secondary
The Characteristics (Including Co-morbidity and Coronary Vascular Lesion Complexity Scoring Referred to as the SYNTAX Score) of the Following: PCI Versus CABG Randomized Cohort, PCI Registry Cohort (CABG Ineligible), CABG Registry Cohort (PCI Ineligible)
Time frame: 5 Years